"Chemical bomb, Chemical bomb. Eyes melt, Skin explodes, Everybody's dead. It won't be long, It won't be long. People gonna run around, losing their heads. A river of blood, Who's gonna live? The earth is tired of human kind. And I think this world, Is gonna wash up in Hell"
A plot device, such as a weapon (usually biological, chemical or nuclear) or a natural agent (like a plague/virus), which drastically reduces the human population in size while leaving a few charismatic survivors. Sometimes Only Fatal To Adults.
In order for a Cozy Catastrophe to remain cozy and small scale, it helps if said cozy catastrophe takes place After the End. It helps to justify the existence of a nearly-deserted but intact urban wasteland that, even if civilization DID collapse in the real world for any reason other than a Depopulation Bomb, would probably still be teeming with people only a few months after the fact. Sometimes major characters have a fortunate random immunity to the widespread plague or chemical/bio-weapon. The use of a biological or chemical weapon may be due to the Nuclear Weapons Taboo.
This is popular for several reasons, largely because it justifies other tropes:
It's more budget friendly to pull off a depopulated future with a single band of familiar survivors and a bunch of faceless enemy mooks than it is to portray a vastly overpopulated future on the other end of the Malthusian Disaster Spectrum. Alternatively, a Depopulation Bomb that doesn't wipe out some 90% of humanity may still justify a Crapsack World.
An underpopulated world in which the Depopulation Bomb only affects humans (or only primates, only mammals, etc...) justifies a return to hunter-gatherer or other primitive lifestyles that can only support relatively small (non industrial-level) populations, thus solving the issue of how the characters feed themselves. May be part of an anviliciousGaia's Vengeance.
Random genetic immunity to the virus-form of the Depopulation Bomb can be a plot device in itself, as an allegory for historical and/or contemporary themes (like racism and segregation) or as the social obstacle for a pair of star-crossed lovers.
Australia, due to its relatively high industrialization, isolated geography, and population of English-speaking Caucasians, is very likely to be the one nation that survives the cataclysm mostly intact, and become a new global superpower, at least in western media. Japan's proximity to the Asian mainland makes its survival dicier, but Japanese authors have this thing about their nation's invincibility, so look for it to be the fortunate land of survivors in anime and other homegrown media.
It may be worth noting that while the Neutron Bomb provides inspiration for many such weapons, a neutron bomb is not a straightforward "It only kills people" bomb. It is a thermonuclear weapon, so this is mostly a simplistic comparison to other bombs with more straightforward Kill Em All purposes. That is, if you actually care about things like scientific accuracy.
Compare the much longer-term Sterility Plague.
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In Sailor Moon Sailor Galaxia releases an attack that causes black lighting to rain down all over earth removing the starseeds of the people of earth. It either kills them or turns them all into Phage. Only the Sailor Senshi are left unaffected.
In Neon Genesis Evangelion, Second Impact. Tidal waves and flooding wiped out the coastal regions while the surviving land was ravaged by shifts in the global climate and resulting famines. It's also been indicated that in addition to lower population and vastly reduced lifespans, the birth rate has dropped dramatically.
Depending on your definition, Third Impact, too. Fans just can't seem to agree just how depopulating the latter's effect was. Instrumentality depopulates as definitely as old-fashioned explosions, but unlike a bomb victim, those caught in it can return to life if they want... it's just that wanting to isn't easy.
In Dragon Ball, Super Buu's Human Extinction Attack, which only leaves a handful of survivors on the surface of the Earth, mainly those skilled and/or lucky enough to dodge it.
Mobile Suit Gundam "Initial fighting lasted over one month, and saw both sides lose half their respective populations. People are horrified by the indescribable atrocities that have been committed in the name of independence..." This occurred as the result of a Colony Drop (which actually wiped out Sydney, Australia, while causing widespread destruction everywhere else), the poison gassing of numerous colonies, on top of the actual battles. Most of this genocide took place over the course of a week or so. It led directly to both sides signing a treaty prohibiting the use of "NBC" weapons ("Nuclear, Biological, Chemical") in warfare.
Rave Master had the Overdrive, which wiped out 1/10th of the world.
The Killitron in Meanwhile kills every single human being not standing inside it when it's activated. It already went off once, and depending on the reader's choices, it may go off again.
A major plot point in Buck Godot: The Gallimaufry is the discovery of an engineered virus that doesn't kill outright, but instead completely eliminates the human sex drive.
In The World, the Flesh and The Devil (adapted from M.P. Shiel's The Purple Cloud, see Literature below), use of a radioactive poison kills most of the earth's population, resulting in a remaining New York population of only three people.
The James Bond film Moonraker had the villain attempting to use a chemical weapon which would kill all humans on earth (only humans; other animals will be fine), to be repopulated with humans from his space station. With him as their leader, of course.
The eponymous menace in Night of the Comet literally erases animal (and human) life on Earth, except for a few people who were indoors/underground — and a few who were "partially protected" who became zombies.
In 12 Monkeys, a man-made virus is released that is so deadly that it kills 5 billion people and, 30 years later, the survivors still have to live underground and can only go outside in environmental suits.
28 Days Later/28 Weeks Later has a spectacularly contagious Rage virus, plus intense aggression by Infected against non-infected. Britain is drastically depopulated by the end of Days, and Weeks has the virus spreading in Europe, thus probably worldwide, setting up the Inferred Holocaust.
Serenity reveals that the Alliance tested an experimental chemical called Pax on a populated planet, meant to curb their more violent impulses. It succeeded too well, causing them to develop severe amotivational disorder, to the point where just about all of them just lay down and died. The ones who survived had the exact opposite reaction to the Pax, becoming the psychotically violent and cannibalistic Reavers.
The Rapture serves as one in the Left Behind film series, the Apocalypse film series, and the Moment After film series.
In L: change the WorLd, Blue Ship, a bio-terrorist group, creates an incredibly deadly virus to depopulate the earth. They stave off releasing it until they create an antidote so that they can survive it, naturally.
In Star Trek's Genesis arc, the Klingons believe the Genesis Device was developed by the Federation to wipe out Klingon populations, leaving planets intact for easy conquest.
M.P. Shiel's 1901 novel The Purple Cloud has the title phenomenon destroying seemingly all human and animal life on earth save for one man...until he learns otherwise.
The Magician's Nephew prequel in the Narnia series treats a magical incantation by the white witch Jadis as this. After ruling her home planet of Charn as a cruel and capricious tyrant with a 0% Approval Rating and on the eve of defeat by her own subjects, Jadis out of pure spite uttered the deplorable word, resulting in the death of every living thing on the planet except herself.
The Day of the Triffids probably belong in here as well. The only people who could really survive were those who kept their sight, or those who were just plain lucky.
In Stephen King's The Stand, A "superflu" kills 99.5% of the population. The post-plague population of the United States is estimated at 1.5 million people. The world's population would be 30 million, equal to everyone on Earth dying except in California or the entire nation of Canada.
Similarly, there's his short story 'Night Surf', which was reportedly the inspiration for The Stand.
Kurt Vonnegut uses this trope a few times, noticeably in Galapagos and "Slapstick". In Galapagos a nuclear war and The Plague wipe out everyone except a few castaways stranded on the Galapagos Islands. In Slapstick, a highly contagious virus made of miniaturized Chinese Communists kills almost the entire population of Manhattan. Various disasters take care of the rest of the world.
Cat's Cradle, as well. When the ice-nine hits the fan it completely annihilates all life on Earth.
In the Mothers' Land by Élisabeth Vonarburg. Far in the future, many children don't survive to adulthood, and the survivors are more than 95% female. Different societies in this world cope with the situation in various ways, but this story takes place in Maerlande, where the official religious explanation is that things changed to the current state as divine punishment on men who misused technology and behaved badly. In this society, men have very few rights and are confined to reproductive duty, being traded between cities to keep genetic diversity up.
The Subtle Knife, seems like this at first, as the Spectres in Cittàgazze target adults and leave them as mindless zombies, so that a city is found completely empty except for a few scavenging children. However there are still a fair number of adults around, but as they're hugely vulnerable and often have to go into hiding, society can barely function.
At the end of The Hork-Bajir Chronicles, Alloran's method of "accepting defeat" by the Yeerks is to engineer a quantum virus which will annihilate the Hork-Bajir population, leaving only a small fraction of the potential number of hosts without directly harming any other organisms.
Fridge Logic questions why he couldn't have targeted it at the Yeerks, you know, the enemy he was actually supposed to be fighting thus decimating their population without harming the Hork-Bajir. In fact, Arbat tries to do exactly this much later on Earth, but the Animorphs stop him because the virus could mutate to kill humans as well.
Old Mans War has a minor Depopulation Bomb in the backstory, as justification for the quarantine of Earth. An alien disease called "The Crimp" caused a third of the planet's male population to go sterile.
John Birmingham's Without Warning has a mysterious energy wave vaporize almost everyone in the continental United States, as well as the bulk of the populations of Canada, Mexico, and Cuba. While not a global depopulation bomb, it still thoroughly depopulates North America.
In Alan Dean Foster's remake of Design For Great-Day, the Solarian Combine is said to have used a Depopulation Bomb on the worlds of a particularly belligerent species; the effect of said bomb being to completely stop them from reproducing. One hundred or so years later, there were no more belligerent aliens. This rumor is enough to bring the Solarians' current target species to the negotiating table, although it's later revealed that they've grown far beyond such crude methods in the intervening centuries.
Jeff Carlson's Plague Year Series: An artificial nanotech virus is released. It kills any warm-blooded animal with a few hours exposure. It's only limitation is that it was designed to shut off at low air pressure - it will not operate at altitudes above 10,000 feet. The only survivors are the people who lived on or managed to flee in time to high mountain peaks, most of which are isolated from each other by lower altitude plague zones. There are two sequels, Plague War and Plague Zone.
In Sergey Lukyanenko's Line of Delirium, the protagonist recalls how, during the Vague War, the Meklar try to wipe out the human race with a virus specifically tailored to destroy spinach. This is because some joker successfully feeds them false information about human dietary needs, claiming that spinach is vital to humans. They spend countless resources creating the virus and then lose many ships trying to seed human worlds with it. After they eventually realize that humans aren't dropping like flies, the shock is so great that they immediately sue for peace. They could've just as easily tailored the virus to kill humans. Of course, from then on, spinach can only be grown in self-contained greenhouses.
In Across The Universe, 3/4 of the population of the Generation ShipGodspeed was killed off in an event called the Plague. The population has been slowly rebounding since then, but the limited gene pool has lead to problems with inbreeding.
The Wild Boy the Lindauzi made virus. Two waves, twenty years apart, and AIDS was said to be part of it. All so they could show up wit a vaccine and get humanity's remains to like them.
In the Star Trek: Deep Space Nine Relaunch, the Trill homeworld is targeted by a series of artificial pulses harmless to the vast majority, but deadly to Joined Trills, who form a priviliged minority. Many of the Joined are killed, with the average citizen completely unaffected.
In one of the Starfleet Corps of Engineers stories, the Miradorn homeworld almost falls victim to a depopulation bomb that was accidentally triggered from the planet's moon. It would have killed 98% of the population (all those Miradorn with psychic links to identical twins), but was halted in time to prevent a significant reduction in numbers.
In Troy Rising, the Horvath drop a series of viruses (and one parasite) on Earth. The parasite is designed to weed out the stupid, being incredibly easy to treat, but fatal otherwise. Four of the viruses target various defects - colorblindness, increased risk of cancer, etc. The last will kill everyone who isn't blond, thus eliminating 90% of the human population. Thankfully, we manage to stop it in time.
The Star Trek: The Original Series episode "Miri" features a duplicate Earth where a genetic engineering project got out of hand and killed off everyone over puberty. The children are still around, because the intended effect of the project was agelessness and it worked fine on anyone it didn't kill.
Another TOS episode, "The Mark of Gideon", had Kirk kidnapped by a vastly overpopulated planet who wanted to use germs in his blood to drop a Depopulation Bomb on themselves. This scheme involves a large amount of Fridge Logic, when one wonders where they found the space to construct a full-scale replica of the interior of the Enterprise.
In the Doctor Who episode "The Sound of Drums", the Master sends the Toclafane from the end of the universe to blast a tenth of the Earth's population.
Done with a vengeance in Jericho, where over a dozen major U.S. cities are bombed with nuclear weapons, leaving only small towns and two major cities standing.
The '70s Made-for-TV MovieWhere Have All the People Gone? has a solar flare causing this.
The BBC has produced two series, one in the 1970s and one in the 2000s, entitled Survivors, which had most of the world population wiped out by a virus which it's strongly implied was artificial.
In an episode of Sliders, the eponymous characters slide into a world where a Middle-Eastern country detonated a bioweapon that specifically targets the Y-chromosome, killing most of men in the world. This gave rise to a new Cold War, this time between US and Australia, the two countries least touched by the virus. Instead of nukes, each tries to "out-breed" the other. The surviving men are rounded up and placed in breeding centers, where they are forced to impregnate multiple women each day. Also, only the most "fit" women are allowed to take part in the breeding program. It seems artificial insemination does not exist in that world.
Professor Aturo explicitly complains about the failure to discover artificial insemination on that world, noting that he could have revolutionized things for them if they actually treated him as more than an animal only good for breeding and actually listened to him.
Stargate SG-1 had two episodes ("2010" in season 4, and "2001" in season 5) about the Aschen, an alien race who conquer worlds by supposedly being nice and friendly and handing out life extending drugs...that sterilize most of the population, letting the Aschen move in and take over after nearly everyone on the target planet has died out.
It helps that the Aschen are extremely patient, willing to wait a few centuries to take over a planet, which becomes yet another farming world for them.
The Aschen can also do this in a more active way. They possess a bioweapon that can be keyed to a particular genome, which kills off most of the species. In the backstory of "2010" they used it on the Goa'uld, and in "2001" they try to use it on Earth when SG-1 figures out their modus operandi. Fortunately the SGC closes the iris in time.
Porcupine Tree: "A Smart Kid"
A spaceship from another star / They ask me where all the people are What can I tell them? I tell them I'm the only one. There was a war, but I must have won. Please take me with you.
It's implied that some sort of Depopulation Bomb is used at the end of Ayreon's "01011001," given the lines like "Washed away by deadly gamma waves" and "All the world's a blazing funeral pyre." And, well, that everyone on Earth is dead afterward.
It was a nuclear bomb, as sung about on the Universal Migrator album, presumably the gamma waves line is there simply because of the Rule Of Cool.
In Exalted Creation was almost reduced to formless chaos as a result of The Great Contagion, followed by the Balorian Crusade.
The Dragon Kings are an even more drastic example. Due to their perfect reincarnation (meaning that every Dragon King regains perfect memories of their previous incarnations after a few decades, tied to their basic mental development), their population was fixed at 150 million. During the Primordial War, enormous numbers were destroyed right down to the soul, reducing them to 30 million. The Wyld incursions caused by the Balorian Crusade whittled this down to a mere 4 million. This means that not only is repopulation impossible, but that many Dragon Kings wind up not reclaiming past life memories (since these will inevitably include vast numbers of people who simply aren't around anymore to a psychology which was never really designed to handle bereavement).
The SCP Foundation has the case of SCP 1322, another world populated by Human Aliens that they found a portal to. Communications and cultural exchange went great until a viral outbreak killed millions of people on 1322's world. The Foundation offered to help and came up with a vaccine that, due to the alien biology of the other world's inhabitants, worked... and rendered everyone infertile. They hate our world now and have been trying to throw a Depopulation Bomb back at us.
The krogan of Mass Effect were hit by a Depopulation Bomb referred to as the "Genophage", designed by the salarians during the Krogan Rebellions. The krogan evolved on Tuchanka, an extremely lethal planet where only massive fertility and hardy physiology made it possible for them to survive, and once they moved off Tuchanka, their numbers, lifespan, and birthrates were so explosive that they needed countless colony worlds to handle their expanding population — including worlds controlled by other sapient species. The genophage reduced krogan birthrates to less than one successful live birth per thousand pregnancies — which, to put things in perspective, would have ideally given them a growth rate still equivalent to a post-industrial society.
On the flip side, it went a bit too far and reduced the krogan to a dying species on a slow decline to extinction and gave most of them (including a party member, Wrex) a Nietzsche Wannabe streak that tends to make them criminals. Their society would easily survive, except they're too fatalistic to try and rebuild.
In Mass Effect 2, If Wrex survived the events of the first game, he'll show up in the sequel, having united the krogan of his home planet under him in an attempt to counter the genophage.
Also the krogan were starting to adapt, so the salarians, namely your party member Mordin, updated the genophage.
Interestingly, the salarians do not view the genophage as a Depopulation Bomb, but rather as a device to control the krogan birthrate to keep them from overpopulating the galaxy. As Mordin so blunty points out, if the salarians wanted to wipe out the krogan, it would have been a hell of a lot easier just to slap them with a permanent sterility version of the genophage instead of the carefully tailored one that allows for "pre-industrial growth levels."
It's worth noting that even with both versions of the genophage, the krogans would have enough young to keep up a steady population. Problem is that they came from a Death World where only the strongest and meanest survive. Thus they're all genetically and culturally inclined towards hyper-aggression. They kept on killing each other as much as ever, but no longer have the super-fertility to compensate.
The aforementioned party member Wrex does tend to focus more on this aspect of Krogan decline than the genophage. He had previously attempted to combat the genophage and gave up, not because it seemed insurmountable, but because other Krogan were seemingly disinterested with the idea of focusing on breeding, or pretty much anything else not related to killing.
Wrex gave up when his own father tries to kill him for daring to suggest that the krogan work together.
The killing of Vigilance by Median in Soul Nomad & the World Eaters turned Haephnes into a very slow version of this trope. Births became decreasingly common and the land slowly became more and more barren as a result of there not being a psychopomp to maintain the flow of souls, and by the time the events of the game comes around the land is little more than a dustbowl inhabited by one of the last generations of sentient life. Gig, of course, greatly hastened this process by killing off most of the population and burning most of the land to a crisp.
Ironically, they don't care about either effect. They only seed planets with Tiberium for one-time future harvesting (once all planetary mass is converted Tiberium, it won't grow anymore) They only attack humans because they're still alive; normally, Tiberium kills off all non-Tiberium-based life before the detonation of a significant mass of liquid Tiberium, which signals them to arrive. Once they do arrive, they judge that humanity needs to be exterminated anyway, as they're apparently criminally insane - GDI and Nod are still fighting each other during a freaking alien invasion, after all.
The Scrin, who themselves are so uncaring about other species as to destroy entire planets for harvesting, called humans "Warlike in the extreme".
'Generals also has the GLA with a variety of bio-chemical weapons and their airburst bomb is in fact a depopulation bomb (it unleashes one of three varieties of a modified Anthrax virus, depending on your upgrades). China gains neutron weapons in ZH which only kill infantry even in vehicles.
The Stone-Like in Radiant Silvergun, which is designed to keep depopulating the planet until humans learn the error of their ways.
The eponymous Halos, which kill all sentient life in the galaxy. They do this in order to kill off possible hosts for the Flood in order to stop them spreading any further than they already have because there's no way to simply kill them off that presumably doesn't destroy every ounce of organic matter in the galaxy. Planets aren't destroyed though, so the method used is never quite explained. They do have a limited range though, which is why there's seven of them.
According to the recently-released Encyclopedia, the Halos work by "sending out a harmonic frequency that targets certain neural cells in sentient organisms". Or something like that.
It that probably somehow overloads and fries the brain of anything with an advanced nervous system though this would requite some serious technobabble to pull off.
It is explained in the Halo universe that the main way the Flood replicate themselves is to infect any organism that has sufficient calcium biomass and a central nervous system, in which humans (and presumably Forerunner) and Elites are perfect specimen. This is possibly the reason you never see Grunts or Jackals infected, as they supposedly do not contain enough calcium in their bodies, and hunters have no central nervous system as they are a hive of worms. You never saw Brutes infected in Halo 2 due to the thickness of their skin but by Halo 3 the Flood got smarter and entered through their mouths. It is explained that other bodies not sufficient for infection or too damaged get used for the creating of the Gravemind. That said, specific cells the Halo rings attack once activated probably have something to do with calcium.
Also note that this was very much a last-ditch plan; the Forerunners tried a conventional war first, and that didn't work.
Lucifer Alpha in Snatcher which results in deaths of 80% of the population in Eastern Europe and Asia.
The Gen-Select bioweapon in Wing Commander IV releases nanobots that kill everyone who doesn't meet the Black Lance's genetic standards. This weapon killed roughly 90% of the population on the planet it was used on.
The big event that the heroes of Chrono Trigger are trying to prevent is the Day of Lavos, when Lavos emerged and laid waste to the world in 1999 (that world's calendar). The human population in 2300 is about thirty people, not counting any captives in Mother Brain's factory.
It is possible to research and build biological weapons in Sword of the Stars. When launched against a planet, each plague missile kills millions of people. Enough of them can quickly depopulate a world with no ill effect to the environment. Another version of the plague makes the target population more willing to join your empire. However, millions still die.
Also, in the Liirbackstory, they are conquered by a vicious race known to them only as the Suul'ka. When they finally rebel, the Liir use their advanced knowledge of biology to genetically engineer a virus designed to kill only the Suul'ka. The virus actually wipes out all Suul'ka in the sector and, as it was previously thought, all Suul'ka everywhere. The sequel reveals that the Suul'ka are Not Quite Dead.
Technically, the manual stated that the Liir used a "bioweapon" and that the specific vector was unknown. The sequel states that the bioweapon is known as "The Black" and is currently the leader of their military. The Suul'ka are actually, very old, very large, and very insane Liir Elders, the Black is an artificial Suul'ka who is loyal to the younger Liir.
The Ultima franchise features the recurring Armageddon spell, first given to the player character in Ultima VI, that effectively destroys all life on Britannia apart from the caster (apart from Ultima VIII and Ultima IX, where it kills the caster as well) and, if they're lucky, a few select NPCs, such as Lord British. Naturally, the games are usually Unwinnable after casting the spell, so pretty much everyone who ever played these games cast the spell once and only once to see what happens, before reverting to an earlier savegame.
In the backstory of Nier, humanity was wiped out by White Chlorination Syndrome, which was the result of Caim, Angelus and the Mother Grotesquerie entering the real world in the E Ending of Drakengard and introducing magical particles to the world. The result is a Zombie Apocalypse that wipes out almost all of humanity, the survivors being converted into Gestalts (what you know of as Shades). The "humans" we see in the game are actually Empty Shells meant only as bodies for humanity's restoration, but thanks to the effort of Nier, that plan's not going anywhere and humanity will be extinct within a generation.
The Facebook game Wasteland Empires is based on this type of scenario, though what type is not stated.
The entire goal of the flash game Pandemic and its sequel is to make one of these in the form of The Plague.
Nukes in Civilization will typically remove 3/4 of the population of a city they're dropped on, and pollute the surrounding region with fallout, making population recovery extremely difficult.
Repeated nuking or nuking a sufficiently weak city will result in that city being removed from the game altogether. Unless it's a capitol city, which are indestructible.
In the penultimate story quest of Fallout 3, President Eden provides you a with a vial of Modified Forced Evolutionary Virus, which will kill all mutated creatures in the Wasteland, including most humans (e.g. those not born in vaults), when inserted into Project Purity. During Broken Steel, if you followed through with the President's orders, there will be people in the clinics dying from the virus, and you yourself die if you consume too much of the FEV-laced water.
In a Sluggy Freelance story arc, humanity in an alternate dimension is almost wiped out by the "ghouls." The only people spared were those onboard one of Earth's many space stations when the ghouls appeared.
The iridium reference is Truth in Television. It was the detection of the rare element iridium at the geologic boundary layer between the Cretaceous and Paleogene Periods that first clued paleontologists in to the possibility that a large asteroid may have struck Earth at that time.
In Homestuck, even if the four main protagonists succeed in The Game and create a new universe, the human race and most other life on Earth will be destroyed by a hail of meteors known as The Reckoning. Only the four of them would survive to carry on the race—and bear in mind these are two pairs of 13 year-old full siblings being told they'll have to repopulate the planet. The kids Take A Third Option and scratch their session, rebooting The Game into a "void session" that at least preserves the possibility of human survival, so long as they eliminate certain outside threats.
In the Homestuck fan adventure A Complete Waste Of Time, the MMORPG META has a policy of determining the players meant to play the game by compiling a list of everyone the server player knows. If anyone on that list does not install the game within one day after the server starts, they inexplicably die. On the planet Seconia (pop. 12.5 million), the ithicans are all connected with each other through some natural network, and thus everyone would know each other on an unconscious level. Unfortunately, only eight copies of the game were made on that planet, and only the owners of those eight copies survived the ensuing near-extinction of the species.
In The Cyantian Chronicles it's stated All There in the Manual that between Akaelae and Campus Safari a super-rabies/zombie type virus wiped out over 90% of the fox population. Which is why fewer of them are villainous in the latter, their tyrannical government is gone and the sole remaining member of the royal family put a death warrant out on Exotica Genoworks for designing the virus.
The Toba Catastrophe Theory holds that 70,000 years ago, a supervolcano in Toba erupted and did this to the human species. The population was reduced to as little as 10,000 people, possibly split up between Africa and India. To give some perspective, that means the entire human race could get good seating at Wrigley Field.
It is assumed that one of the men of Hernán Cortés who was killed as the Spainards had to flee the Aztec capital was infected with smallpox. When the Aztects disposed of the body, they came in contact with the virus, which started a pandemic that spread through all America and eventually killed over 90% of the native population. Some years later, Europeans colonized an almost entirely depopulated continent.
The Noble Savage trope comes almost entirely from this. The pre-contact Indians were very much civilized and had enormous, beautiful cities that would have been the envy of the Old World. The smallpox (and later typhus, measles, influenza, etc.) came and all the knowledge and infrastructure needed to support those civilizations was Lost Forever.
Evidence suggests (and this troper is not trying to be racist) that it was actually a black slave that came in the expedition of Pánfilo de Narvarez, who tried to arrest Cortés. The epidemic was so bad even the tlatoani (emperor), Cuitláhuac, died of smallpox. It didn't help either that when Tenochtitlan was seiged, the Spaniards and natives (more that 90% of Cortés's men were allied tribes) dropped corpses on Lake Texcoco to infect the water supply.
Strategic nuclear weapons were designed to destroy large areas of the enemy's infrastructure, such as cities. During the Cold War the United States, Soviet Union and their allies were all pointing nukes at their enemies' cities, and over 70% of those countries' populations are urbanized.
Biological and chemical weapons, unlike nukes, are intentionally designed to devastate civilian populations and, more importantly, disrupt the enemy's supply chain and divert resources including vital medical supplies and personnel from the front lines.
It should be noted that biological weapons are the only weapons which are fully banned by international law.
Cobalt bombs. Cobalt absorbs radiation and transforms into the radioactive Cobalt-60 isotope, which falls over a large area as fallout, potentially rendering a swath of land uninhabitable for some years. However, the world-destroying cobalt superbomb feared in pop culture is a grossly exaggerated fantasy, and the only attempt at building a cobalt bomb ended in failure. It would certainly be a Depopulation Bomb for many miles from the impact site though.