The Historical Fiction manga Anatolia Story has as one of its subplots a terrible plague that affected the Hitite empire. In actual history, the plague raged in Hattusha for some 20 years and killed a large portion of the population, including King Suppiluiuma, King Arnuwanda, and Gassalawiya, Mursili's wife that Yuri's character is partially based upon.
In Rurouni Kenshin, it is revealed that Shinta later called Kenshin was the only survivor when his village was hit with cholera. He was taken in by Hiko Seijuro, and trained in the art of swordsmanship.
The Gendercide plague Redface Pox in Ooku: The Inner Chambers, that only affected males and left feudal Japan a (predominantly) Lady Land. Bears are carriers for the plague, apparently.
The Ebola Gulf-A from BatmanContagion, originally unleashed in Gotham City by the Saint Duma's Order but later revealed to have been created by Ra's al Ghul
The Legacy Virus killed off a few mutants. One strain of it was capable of infecting ordinary humans too; Moira McTaggert was the most well-known non-mutant victim.
In Nth Man: The Ultimate Ninja , after the Soviets and the United States launch biological warheads at each other, a powerful Reality Warper tries to neutralize them. Instead, he turns the lethal virus into a nonlethal mutagen that turns infected humans into disfigured "moots" with a taste for flesh.
One of the members of the Green Lantern Corps is actually a sentient smallpox virus named Leezle Pon, who stays out of meetings because it would infect the other Green Lanterns. The Sinestro Corps, on the other hand, has its own sentient virus known as Despotellis, who is responsible for killing Kyle Rayner's mother.
The Hourman Virus spread by Solaris in DC One Million was particularly insidious. Caused by Nanomachines, it acted like both a biological virus and a computer virus, and could be spread to each type of victim by the other type. And it was capable of wiping out humanity in twenty-four hours.
The Glee and Avatar: The Last Airbender Fusion FicSolar Winds has a mysterious plague spreading across the entire world. Most, if not all of the still-living victims have been quarantined on an abandoned island in the Fire Nation. Fire Lord Sue plans to get rid of the plague by simply blowing up the volcano on the island.
The Omega virus from The Omega Man. It kills most of the human race, and turns most of the rest into zombie vampires.
The virus from Twelve Monkeys, which is virulent enough to force the remaining survivors underground.
While Mimic is about Giant Mutant Bugs, it's a child-killing Plague which prompts the bugs' creation in the first place.
In Cabin Fever, the flesh-eating disease will eventually reach pandemic levels.
In L: change the WorLd, a terrorist group create a virus that is a mix of ebola and influenza, highly contagious, and quick to mutate. Naturally finding a cure before it wipes everybody out is the main plot of the movie.
The unnamed virus in the 2009 film Carriers has already decimated humanity when the movie starts.
The Bay revolves around a coastal town being almost wiped out by a disease caused by a mutated fish parasite.
Michael Grant's Gone series. There are two of them in the appropriately named Plague.
Geraldine Brooks' Year of Wonders. However, the protagonist wasn't trying to find a cure (it was the Black Death), rather, her village was purposely isolating itself in order to stop the plague from spreading more than it had to. Something of a Heroic Sacrifice... Most of them died.
The Plague, a novel by Albert Camus, is about a plague outbreak of the Algerian city of Oran.
The descolada in Orson Scott Card's Speaker For The Dead and Xenocide. Interesting in that while it's fatal—and nastily so—to Earth life, it is absolutely vital to the ecosystem of Lusitania, necessitating an approach to the disease that didn't eradicate the pathogen entirely.
In Stephen King's The Stand, a deadly variety of influenza, manufactured by the US government, is accidentally released and wipes out 99% of the world's population. The disease is called "Captain Trips", among other names.
Also featured in King's early short story "Night Surf" (appears in the collection Night Shift), though the pandemic is natural here.
In the short story "The Ship Who Mourned", a plague has wiped out most of a planet's population. The handful of survivors of this disease are either immune or are left paralyzed. Helva supports Theoda in an attempt to demonstrate that physiotherapy may be effective for the latter.
Subverted in Android at Arms: The "epidemic" which led to the planet being quarantined - and thus cut off from any possibility of further outside interference in an ongoing civil war - was actually due to one of the rebel leaders' poisoning of the water supply of the main mercenary outpost.
Breed to Come: The story opens After the End; the plague that wiped out the humans (called the Demons in-story) led to the development of intelligence in several other species, including that of the protagonist.
Dark Piper: The planet Beltane, a lightly settled planet dedicated to biological research, developed some biological weapons, as some would-be invaders learn to their cost.
Ordeal in Otherwhere: An epidemic has decimated the Cult Colony on Demeter, leaving few male survivors. The protagonist, the now-orphaned daughter of the colony's education officer, is on the run as the story opens, since the survivors have become viciously xenophobic and she is an outsider.
The novella and short story "Outside": All the adults died years ago.
Plague Ship: Fear of this trope means that the titular ship can't seek help through legitimate channels, as they will be destroyed without trial if their status is known.
The Zero Stone: In the Back Story, a plague ship crashed on planet, and since they both survived, his parents did much better after than before. Also, he comes down with something, which causes the Free Traders to panick, because they might be labeled a plague ship.
The Red Death in Edgar Allan Poe's "The Masque of the Red Death", which appears to be a cross between Tuberculosis and the Bubonic plague, although Ebola probably fit the bill too.
The germ-bomb used by the Soviets on the Midlands and spread by wind to cover 2/3's of England and Wales in Breaking Glass, by Brian Morse.
In the X-Wing Series the Krytos Plague is engineered by Imperial elements to kill only nonhumans. The Imperial throneworld, previously known as Coruscant, is infected with the plague just before the Rebel Alliance takes it, so that not only will nonhuman populations be decimated, but the Alliance will have to spend limited resources treating the victims, and nonhumans will be bitter at perceived favoritism.
Galaxy of Fear: The Planet Plague. The people of Ghobindi were wiped out long ago by a big plague, and an Imperial interest on that world is looking into tailoring a new one from samples which turns people intoBlob Monsters.
In Hermann Hesse's book Narcissus and Goldmund, while Goldmund is wandering about Europe, the Black Death breaks out, and he meets several characters who lives have been transformed by the plague, Robert and Rebecca, to name a few.
Subverted by Harry Turtledove in his short story Nasty, Brutish And..., part of a wider sci-fi universe. The Foitani, a race of galactic conquerors, find out which planets are likely to later produce potential enemies and hit them with an engineered virus that will constantly mutate to ensure their life forms will never be free of it. However, it turns out that Earth was one of these planets, and the virus turns out to be...the common cold.
Possibly the original world-killing-disease novel is Earth Abides by George R. Stewart from 1949, where humanity is cut down by a plague once mentioned as a kind of "super-measles".
The Fourth Empire from Empire from the Ashes—a huge, incredibly-advanced, galactic civilization—was completely annihilated (only Dahak's crew and an isolated planet (Pardal) in the third book were shown to have survived) by the accidental release of an experimental bio-weapon. Said weapon halted the critical chemical reactions of any life it encountered, rapidly evolved, had a very long dormancy period, and could survive for centuries outside of a host. Holy shit.
In a nonlethal variant, H. G. Wells' "The Country of the Blind" is set in an isolated Andean community where a disease that targets the eyes had blinded the entire population long ago.
In the Farsala Trilogy, a "swamp fever" that regularly decimates the Kadeshi population is mentioned. Kavi and Soraya use it to their advantage when they are captured- they promise that, if they are released, they will convince the Suud to find a cure.
The Changeling Plague features the titular disease.
The Tunnels series has Dominion, a strain of influenza genetically engineered by the Styx into a super-plague that will kill everyone on the planet's surface, allowing those living Beneath the Earth to rise up and take their place.
In Robert E. Howard's Conan the Barbarian novel The Hour of the Dragon, a plague is used to eliminate a king and his immediate heirs, to allow his young brother Tarascus to ascend the throne. Since the plague stops with the king's death, Tarascus is acclaimed as the chosen of the gods.
In Ted Dekker's Circle Trilogy, the Raison Strain.
Colas Breugnon has a plague halfway through the book. The protagonist, always carefree, accidentally catches it and nearly dies, but still keeps his cool—except for when his grand-daughter nearly dies, and when his old house and everything inside is burned down by other townspeople for fear of plague.
The Roman Mysteries features an historic pandemic that starts at the end of The Twelve Tasks of Flavia Gemina and becomes on of the main plot points of The Enemies of Jupiter.
The Sickenesse in Septimus Heap is a plague that was brought forward by Ghost Queen Etheldredda's pet animal the Aie-Aie and plays a background role in Physik.
There are two major examples in the Warrior Cats series: greencough, a deadly, contagious pneumonia-like sickness; and an unnamed sickness that crops up in ShadowClan from them eating rats (later referred to as ShadowClan's Great Sickness): it only comes once in a great while and wipes out a good chunk of the Clan, and it doesn't have a cure until Cinderpelt discovers one.
The fourth in the Circle of Magic series, "Briar's Book"/"The Healing in the Vine" deals with a plague sweeping through the city, and the main characters' work to heal the sick, discover its origin, and try to find a cure.
The works of Max Brooks involve a virus - named "Solanum" in The Zombie Survival Guide and unnamed in World War Z. In either case, the virus is present globally - in the Guide, it's present in low enough levels to escape detection by the public at large, but not so much in World War Z.
Touched upon in Orson Scott Card's Pastwatch: The Redemption of Christopher Columbus. In the original timeline, Columbus didn't go to America, but went east on a Crusade. As a result, a ruthless Mayincatec empire forms that soon encounters Portuguese sailors, develops immunities to their diseases, and proceeds to conquer an unprepared Europe— which has no defense against the American diseases. An interesting reversal of how it went in our history. A more benign version is spread among the new, less bloodthirsty Mayincatec and Caribbean cultures by the time-travelers in the end, giving them immunity to European diseases.
The plot of the fourth book of The Sword of Truth is driven by a magical plague unleashed by the Imperial Order.
Just about every ailment in the world of Clocks that Don't Tick has evolved to the point of causing near-certain death. Thereíre super AIDS, super flues, super rabies, and thatís just scratching the surface.
The Bliss Virus in the Doctor Who episode "Gridlock".
"The Empty Child/ The Doctor Dances" has an interesting version: "physical injuries as plague," as Dr. Constantine puts it.
In the Torchwood episode "End of Days", it was feared that people coming from other centuries would spread diseases for which the modern population had no immunity. Interestingly enough, although there were cases, the actual bubonic plague was the least of their concerns.
The disease from "The Naked Time" (and its sequel "The Naked Now") is apparently non-fatal, but is highly contagious and, in both episodes, adversely affects the crew in the midst of a disaster which could destroy the ship.
The macrovirus in the Voyager episode "Macrocosm". Especially nightmarish because of the monsters that exist solely as vectors, and are produced by the comatose sufferers.
Also "The Phage," an entire alien species struck with a plague, and is forced to steal body-parts from other species. Their weapons teleport organs right out of you. Fortunately, the only major character it happens to could be kept alive until his lungs are retrieved. If you're a Red Shirt you may not be so lucky - Torres and a nameless crew member are captured, and their captor comes back wearing the Red Shirt's face to replace his own diseased skin.
In Star Trek: Deep Space Nine, the Dominion infected an entire planet which resisted them with a plague called "The Quickening" (after the final deadly stage of infection). Everyone is born with it, most die in childhood, but enough people survive to adulthood to reproduce and keep their population from entirely dying out even after a few hundred years. It has replaced all other forms of death on their planet and left their society incapable of maintaining their previous level of technology and infrastructure ( in large part because the disease escalates much much faster around any kind of electro-magnetic power source), turning what was once a space-faring civilization into something resembling the Dung Ages. The look on the people's faces when Dr. Bashir discovers a vaccine that will prevent future generations from being infected by inoculating them in the womb is something of a Crowning Moment of Heartwarming, even though he feels that he has failed because he can't save the generation that is currently infected.
The Federation's "Section 31" also created a plague to kill the Changelings and win the war. Dr. Bashir was also involved in countering this plague in the series' last season.
Reality show The Colony is about ten contestants trying to build a working, self-sustaining colony after a fictional worldwide viral outbreak kills off the majority of the population.
The Tribe, a show based around a world in which a mysterious virus wipes out all adults seemingly overnight, leaving the children and teenagers to fend for themselves.
Earth: Final Conflict had some sort of plague on humans that was caused by the Taelons after their arrival on Earth.
The plague that almost killed the Ancients in the universe is an important part of the setting. It wasn't enough to kill them all, but the first time they encountered it they said "screw it, we're out of here".
The same or a similar plague was used by the Ori against unbelievers in the Milky Way. It was the first and only time when a weapon of mass destruction was successfully used against Earth in the primary universe.
"The Night of the Plague" and "The Night of the Gruesome Games" from The Wild Wild West involve the main characters attempting to stop the spread of a deadly disease.
In Exalted's backstory, a plague known as the "Great Contagion" wiped out 9/10ths of all life in Creation. The really scary part? No one knows why it didn't finish off the last tenth, which is what it was designed to do.
In TravellerIntersteller Wars the Vilani not only find that they cannot cope with Terran diseases but that Terrans can. Some of them surrender just so Terran Medics can arrive faster.
The card game Nuclear War features the SuperGerm card, which moves among all of the players and attacks their populations in turn.
Actually, that's SuperVirus, from the expansion Nuclear Retaliation. SuperGerm just kills 25 million in one shot.
The VITAS plague cut back the planet's population by about 1/4, then another 1/10, in the future timeline of the Shadowrun game setting. Ironically, the second outbreak actually helped society; it came not long after goblinization first broke out (turning people into orcs and trolls), and seeing orcs and trolls catch VITAS made it clear that they were humans, not some sort of body-stealing monsters.
In Pandemic (where you fight disease, not like in the flash game of the same name, where you are the disease) you have not only one, but four (or even five with the expansion) plagues.
Kinda. Blight is actually a whole set of related diseases that aren't really all that deadly (and there's no need to search for a cure, since there already are known cures. They're just somewhat more expensive/magicka-draining than the cures for common diseases). Corprus is incurable and has horrific effects, but is actually fairly non-infectious, for the most part — it doesn't really spread without someone's deliberate action (of the 'constantly repeating it' sort, not of the 'break one canister and whole world is infected' sort).
The entire plot of Left 4 Dead revolves around this - the main characters are some of the only people with natural immunity to The Virus that turns everyone else into crazed killing machines. There is no cure - they can only run for their lives.
It's worse than that. They're asymptomatic carriers, like Typhoid Mary.
Plague Inc for iOS started out as a Pandemic clone but, a number of updates later, has surpassed the original. One of the main changes is that, in Pandemic, the world searches for a vaccine, which can be a moot point if everyone is already infected. In Plague Inc, the world searches for a cure, which is distributed within days to everyone in the world and is a nearly-instant game over.
Persona 3 had the city believe that Apathy Syndrome was caused by a plague.
In Persona 4, the fog that envelops Inaba by the end of the year and causes every last (non-named) inhabitant to slowly go insane with nihilism at best, or collapse in inexplicable, incurable illness at worst.
The Forsaken are also the result of the Scourge's Plague. As well as the majority of most undead.
The "Corrupted Blood Plague" was an incident where players used pets to collect a debuff capable of spreading to nearby players and NPCs and then unleashed them in cities. Entire cities were depopulated.
Pathologic is basically a survival game in an infected town.
The Trauma Center series has a man made one in the GUILT and Stigma diseases (Though the latter is due to technology gone wrong) Trauma Team kind of follows in the tradition by having the Rosalia virus, which is comparable to the Ebola virus, only deadlier and with a dose of Ax-Crazy. The last arc focuses on a widespread outbreak of the disease.
It's small potatoes compared to the rest of the plot, but there's a plague on Omega in Mass Effect 2 which is rapidly lethal towards everyone but vorcha and humans, the latter of which are accused of creating and spreading it. Vorcha are seen as too short-lived and unintelligent to do anything of the sort. Professor Mordin Solus, who develops a cure, believes it was created by the Collectors.
Prototype deals with a Synthetic Plague infecting Manhattan and turning everyone in the city into mutated monsters under the control of Elizabeth Greene. It turns out that the protagonist, Alex Mercer, is the result of the original Doctor Alex Mercer's enhancing of the original "Redlight" plague virus into the current "Blacklight" virus, up until the point where he was shot and killed and the virus infected his corpse, resulting in the entity that would become the avatar of the Blacklight virus that thinks it is Alex Mercer.
The Plague, referred to by name, is present in both inFAMOUS games, but is a significantly larger threat in the second. It's caused by ray sphere radiation, a contagious plague that's 100% lethal, but conduits are immune to it, choosing to ease nature along and create a world of superhumans or sacrificing yourself and every other superhuman to cure it is the penultimate karmic choice of the game.
Sword of the Stars features a number of different bioweapons that ships with Biowar modules can deploy against enemy planets. Allowing a player to kill everyone in the colony with minimal damage to infrastructure and terraforming. A specialty of the Liir.
Though the Zuul in the first expansion are both immune to bioweapons and unable to research them.
Plagues can show up as random events in the Conquests expansion to Civilization III. They kill a number of citizens in a city and only disappear after a certain number of turns; building certain city improvements can reduce their impact or eliminate them entirely.
The "Prometheus Virus" of Sid Meierís Alpha Centauri works essentially the same way as the Civ III Plagues; again certain base facilities (Research Hospitals and Nanohospitals) prevent them. Also, your Probe Teams (read: spies) can spread the disease as a form of biological warfare.
In Virtue's Last Reward, there's radical-6, a disease that slows the brain function of its victims and eventually causes them to become insane and suicidal. Over the course of the game it is gradually revealed that the game takes place many years after the player thought it did, after the pandemic has killed most of Earth's population, and that the point of the game is to fix that.
Pharaoh: a non-specific plague is a possible disaster/divine punishment if you don't ensure good citywide health (access to physicains and clean water) or piss off Bast. It instantly kills a group of houses, and releases walkers that spread their infection across the houses they pass.
In Medieval 2: Total War, cities can suffer from the plague when they grow too large, but at a certain point in the timeline, the Black Death strikes and nearly all cities have a few years of plague. It is possible for units to survive for some time while infected, allowing them to spread the plague when they conquer uninfected cities or for spies to (accidentally, ahem) introduce it to cities they infiltrate. Your economy tanks meanwhile, though it may well recover after as half your army is suddenly no longer pestering you for wages.
A plague wiped out 99% of all human males in the universe of Angels 2200. A plague we find out was created by Earth's central government as a way to pacify the off-world colonies.
A big part of Lands of Red and Gold concerns the fact that the Alternate History Australian civilisation has its own pandemic diseases which make their way back to the Old World after contact is made in the early 1600s, basically decapitating half the political leadership of Europe among other things.
The Chaos Timeline has the Black Death, happening somewhat later and spread through longer time than in our world.
In the Futurama episode "Cold Warriors", the plague is the common cold, which was erradicated in the 25th Century but reintroduced by Fry after a dormant strain of it was reactivated. Now with no vaccine or natural immunity, drastic measures are taken, mainly quarantining the entire island of Manhattan and hurling it into the sun for good measure.
The Plague of Athens in 430 BC, probably typhus or typhoid but possibly a hemorrhagic fever distantly related to Ebola, struck during The Peloponnesian War, crippling Athens' ability to fight the Spartans, killed Pericles, and led to general anarchy on the streets.
The Antonine Plague in AD 165-80, probably smallpox but possibly measles, left Rome's legions undermanned, setting up a century of nearly fatal external threats. In addition, the plague may have caused the death of Marcus Aurelius, the last of the "Five Good Emperors".
The Plague of Cyprian around AD 250, essentially a repeat of the Antonine, and also claiming the life of an Emperor.
Justinian's Plague, almost certainly the same Yersinia plague that caused the Black Death, absolutely devastated the Roman and Persian empires. It was one of the main reasons the intact Eastern Roman Empire wasn't able to reestablish the Western Empire. Later recurrences of the plague were probably one of the reasons Islam spread as far as it did.
The Black Death, also Yersinia plague, began in China and had spread to Europe by the 1300s, killed a sizable fraction of the Eurasian population: estimates vary wildly, but some place the death rate as high as 60%. Europe's population would not recover for 150 years.
The H1N1 flu pandemic of 1918, which may have had an even higher death toll. Modern estimates peg the death toll at 100 million people, or what was at the time five percent of the world population. (By contrast, the death toll for World War One (which was raging at the same time) was "only" about 10-15 million.) Unusually, this strain of flu hit young adults and adults the hardest—children and older people did OK. It's thought that it killed by causing a cytokine storm, a fatal overreaction of the immune system. Because of this flu it was the second world war that was the first in history where more people didn't die afterwards of disease than died during the war.
91 years later, the H1N1 only did a minor a dent on worldwide death statistics with "barely" 284,500 dead, thanks to 2009's medicine and the swift measures taken worldwide to prevent its spread. The memories of 1918, however, were still enough to keep the entire world scared, and indeed many people thought it would be the end of the human race. 
1918's H1N1 killed 22% of Fiji within two weeks. One scientist at the time said "If the epidemic continues its mathematical rate of acceleration, civilization could easily disappear from the face of the Earth within a matter of a few more weeks."
Nobody knows just what the population of North America was pre-contact, but it was a lot smaller just a few generations later. Some estimates range to up to 90% of the pre-contact population was killed by one or more European germs. Culprits included smallpox and various "childhood" diseases from Europe. It's believed that the European's contact with farm animals made them resistant to the diseases they carried.
Speaking of smallpox: while people in the Old World had had millenia to develop resistance to it, and while it was more endemic than pandemic (it existed as a persistent disease in most places rather than appearing in brutal and massive outbreaks), it still wasn't exactly harmless: it is estimated that as much as 500 million people died from smallpox in the 20th century alone.
Throughout history, disease epidemics killed far more people than wars ever did. It was a source of horror for people, as a plague could strike without much warning and kill a majority of the people in the village. The phrase "a pox on your house" may seem quaint to us now, but it was essentially wishing that a person and his entire family would be killed by a plague, which was a very real possibility. This is one reason children in Medieval Europe were fostered to other families at an early age: if (say) an epidemic of diphtheria struck your community, you could lose all your children in the space of a few days. Fostering children in another community at least helped to ensure that some of your descendants might outlive you.
War tends to foster quite a nice set of plague conditions: disruptions of infrastructure, especially anything that will reduce people's ability for nursing; overwork because all the men are away fighting; disruption of food supplies leading to a poorer diet; dead bodies lying around; people resistant to the bugs in one area travelling to a second area where they are not resistant, picking up the bugs and then travelling to a third area where no one is resistant.
Ebola is a recent example. There are no drugs to directly treat it, a vaccine that works on humans has yet to be developed, and it is so contagious the only real way to prevent its spread is to quarantine large areas. Thankfully, it had been confined to Africa...for now. An important point is that Ebola is so virulent that it kills its victims before they can get very far—it's not airborne and transmission is easily prevented by proper hygiene, which tends to keep it in isolated villages (until the 2014 outbreak).