After failing to make a good comeback joke against Brian, Stewie goes back in time to redo it, before continually messing around with Brian. Eventually, Brian catches him inside the time machine. In fighting over its controls, they are accidentally transported out of the space-time continuum, where the laws of physics do not apply and where the return pad cannot get them home. Stewie decides to take a risky effort to overload his return pad to bounce them back into the space-time continuum. Stewie later determines that he was the cause of the Big Bang, because the background radiation that created the universe matches the signature of his return pad all due to the temporal predestination paradox causality loop.
When Stewie obtains his plutonium to power the return pad, Bertram learns of the time machine and sneaks into the Griffin house to kill Stewie's ancestor in order to prevent him from ever being born. Unfortunately, as Stewie and Brian discover, by preventing the former from being born, then Stewie would not have been able to start the Big Bang, thereby creating a paradox that begins to wipe everything from existence. Stewie explains this to Brian and says that they will have only one shot at getting back to the present since Bertram took the return pad with him. Brian and Stewie then go back to fifteen minutes before Bertram arrives in the past to stop him from killing Stewie's ancestor, revealed to be Leonardo da Vinci. Stewie guesses that since he and Bertram share the same father but have different mothers, Leonardo da Vinci must be an ancestor from Lois's side of the family, or else Bertram would be erasing himself as well if he killed Leonardo da Vinci.
When Bertram arrives in the past, he throws a knife at Leonardo da Vinci, forcing Stewie to block the attack. Stewie then tries to kill Bertram with the knife but Bertram hits Stewie before he could do so. He then uses Leonardo's winged flying machine to fly away. Since Stewie needs the return pad to get back to the present, he uses Leonardo's ornithoper to chase Bertram, and ends up battling in midair with him. Stewie shots a magnetic missile at Bertram but he jumps out of Leonardo da Vinci's invention and activates his parachute so he can safely fall to the ground. Bertram takes a crossbow and has Stewie, Brian, and Leonardo at a crossbow point. Stewie tells Bertram that he created the universe and that if he is erased, the entire universe will disappear forever. But Bertram says that to him, erasing Stewie is worth destroying the universe and shoots Leonardo in the chest with a crossbow. In rage, Stewie shoots Bertram in the chest and head with the same crossbow, killing him.
Despite the fact that Leonardo is dead, the universe is still existing. Stewie then concludes that he must be his own ancestor. He sends Brian back to the present, where a letter from the Holy See Vatican arrives, detailing that Stewie has buried himself in a cryogenic tube underneath the Griffin household. Once he is unearthed and thawed, Stewie informs Brian he put his DNA into a syringe and injected it into Leonardo's girlfriend (multiple times). Stewie brings back a candle from Leonardo's time, leaving Brian (who would have rather had him bring back one of Leonardo's original notebooks) annoyed.
!!Tropes related to the episode:
* ApocalypseHow: Class X-4. Had Bertram killed Leonardo Da Vinci, Stewie would never be born, thus the whole universe would've been erased.
* AssholeVictim: Bertram
* DidntThinkThisThrough: Averted. Bertram makes sure to target one of Stewie's ancestors on Lois's side of the family.
* DisproportionateRetribution: After Brian makes a queer joke at Stewie, the latter proceeds to use time travel to screw with every uplifting moment in his life.
* KickTheDog: Bertram killing Leonardo Da Vinci, even after Stewie told him that doing so would destroy the entire universe.
* LameComeback: Stewie doing this is what kick-starts the plot.
* LesserStar: Brian thinks he deserves some credit for the creation of the universe. Stewie describes him as the Garfunkel of the universe's creation.
* MyOwnGrampa: Stewie became his own ancestor after Leonardo died.
* OmnicidalManiac: Bertram was an unintentional example as he tried to erase Stewie's existence, which would consequently erase the universe. However, even after Stewie warns him what will happen, he decides to do it anyway.
* PreMortemOneLiner: "Hey, Bertram, what's your favorite kind of bottled water? Mine's arrowhead."
* RevengeBeforeReason: Bertram is perfectly okay with the destruction of the universe if it means killing Stewie.
* ShoutOut: Brian laments Stewie having to stay behind, but then [[Film/BackToTheFuturePartII he receives a note from the past with specific instructions]].
* StableTimeLoop: Stewie created the universe, the universe in turn created Stewie so he would create it.
* TookALevelInJerkass: Bertram. In his first appearance, he and Stewie become friends. In his second, he gets along with Stewie as often as he fights him. But here, he's a true KnightOfCerebus, who becomes more hellbent on erasing Stewie than ever, even after being told that it would end the universe as well.
* WhatHappenedToTheMouse: We didn't see what happened to Leonardo's body, but it can be assumed that Stewie buried it somewhere.
* WorthIt: Bertram says it before killing Da Vinci.
* WriteBackToTheFuture: How Stewie tells Brian about the cryogenic tube.
* YouFool: Stewie angrily yells this at Bertram when he kills Da Vinci even after being told the consequences.