- In Opplopolis the word "marvedyne" is seen, read or overheard repeatedly in ominous contexts (including the very first panel of the series), spurring many of the characters to actively pursue its meaning, which is still unknown but appears to have something to do with a secret society of aristocrats. Real-world google is no help.
- Marsh Rocket features a Pulp Fiction-style suitcase that drives the plot. It is revealed to contain tax papers for the IRS.
- In Kevin & Kell, the original Danielle has disks with all the important data for "Rabbit's Revenge", an underground group with terroristic tendencies. The disks are shown in the June 21, 2003, strip, labeled "McGuffin disks".
- In Homestuck Calliope actually calls her Juju this when she refers to it as such. Considering it later does actually have a purpose, however, the status of this item changes somewhat.
- In Absurd Notions, The Legendary Rock of Rama Lama is initially a MacGuffin (illustrated by Warren's remark), but ceases to be that when the players refuse to accept that.
- On the cast page of Erfworld, the Arkenhammer's occupation is actually listed as "MacGuffin". (Strictly speaking, it isn't one: the Arkenhammer — or more precisely, the dwagons that have been tamed with its power — are critically important to the plot.) It also cracks walnuts rather well, though they occasionally turn into pigeons instead. Sometimes you need to tame a dwagon. Sometimes you just need to bust a nut.
- For the first book, the Arkenpliers fill this role a little better, being a divine artifact Stanley wants to get his hands on. Its only ability is to turn uncroaked to dust with a single strike, which is more of a cool side benefit than a real plot point. In the second book however, it is not a MacGuffin. At this point, its powers are awakened, and it is no longer just an irrelevant object being sought.
- Issue #23 of Nodwick did this while simultaneously parodying The Lord of the Rings. The title character finds "This One Ring" and his employers force him to go on a long quest to destroy it. When the history of the ring is told, it's made clear that the ring does absolutely nothing, but everyone except Nodwick acts as if the ring had infinite power.
- Ancient sacred relic #7 in Hellbound.
- Parodied in MegaTokyo. Early on, Largo blows all his cash on a mysterious "cool thing". The exact extent of its abilities is never revealed, but it apparently at least has the power to call forth a legion of cardboard robots Largo created. Also joked about in one of the books, where author Piro comments that even he doesn't know what it does, and "Shirt Guy" Dom comments that the instant they figure it out, it'll be sold at the site's store within two weeks.
- Lampshaded in The Order of the Stick, Xykon informs Redcloak that he only cares about the "MacGuffin", referring to the rift gates.
- In Goats, Diablo convinces Bob and Neil to become art thieves:
Diablo: Ah. Here we are. The "Holy MacGuffin" is on display at the Metropolitan Museum of Art.
Neil (or Bob): What's a MacGuffin?
Diablo: It's not really important.
Neil (or Bob): It sounds like a species of flightless waterfowl.
Bob (or Neil): Or a breakfast sandwich.
- The glowing ball in Autumnside is a MacGuffin which is at least semi-sentient.
- In Captain SNES: The Game Masta Alex is given a Mystic Mouse, which is supposedly an extremely powerful item. But he doesn't know how to use it and openly refers to it as a "MacGuffin".
- The beginning of Gunnerkrigg Court, Chapter 23: "Terror Castle of the Jupiter Moon Martians", features a MacGuffin parody. Within the simulator, the students are tasked with retrieving an Ancient Artifact from the aforementioned Terror Castle. Andrew Smith's order-inducing powers rewrite the simulation to make the artifact appear at his feet, thus ending the plot before it could even start, much to his and the other students' chagrin.
- And the readers' who where cheering at the idea of a new spacemonauts tale
- As in the original Final Fantasy, 8-bit Theater's elemental orbs of light are the four pillars upon which the world depends upon which the Light Warriors have to collect for reasons unknown to them.
- Speaking of Final Fantasy, the Warring Triad from Final Fantasy VI. They're just petrified gods that are introduced out of nowhere to give Kefka godlike power. Then Kefka makes you fight them later on because...he...can...? Suffice it to say, the conclusion would have been no different if it were a magic paperclip.
- The Narshe Esper is also initially an example of this, but bigger MacGuffins later on greatly overshadow it.
- The Crystals of Light in many earlier Final Fantasies (such as IV and Mystic Quest) are also examples of this.
- Lampshaded in A Girl and Her Fed, though here's to hoping that they're not what we'd traditionally call a MacGuffin, as they had better explain some things. Unless this is a hint from the writer that they won't...
Girl: Damn, we're juggling a load of MacGuffins. And I've heard MacGuffins are insanely high in calories... Get it? Muffin? MacGuffin?"
- The Staff of Time in Umlaut House 2. Saundra even refers to it as "that distant-future MacGuffin Peggy's carrying."
- In Endstone's Backstory the Endstone was this to Jon at first -- he wanted it only as bait.
- Lampshaded in Neko the Kitty. Magic black cat Poe has enlisted the aid of some of the human cast to help him track down his witch
Alice: Surprise! I was paying attention! Now let's go get that Horcrux!!
Alice: Whatever, it's a maguffin. Now let's go get that treasure!
- Troops Of Doom has Legotech, a mysterious technology that runs on Clap Your Hands If You Believe.
- In Far Out, a robot has a place where a star is obviously missing. They are looking for it.
- El Goonish Shive has the Dewitchery Diamond, a Mineral MacGuffin that is responsible for the existence of one of the main characters and the instigator of two story arcs.
- The Fourth has minor ones throughout that drive sub-plots, but the over-arching one is the Hereditary Curse that Skärva is driven to overcome.
- Corgi Quest has two so far. First is the Encorgidion, a magic book that Bonabelle is searching for. The other is a magic sword that Lord Common sent Kousuke to retrieve. The necromancer also wants the sword in order to summon and bind one of the most powerful demons ever known.