The film opens at the Quahog Community Swimming Pool. Encouraged by Peter and Lois to take swimming lessons, Stewie meets the star pupil of the class, Brad. Jealous, Stewie decides to try and outdo him in a swimming race. He nearly drowns in the process, while Brad finishes in first place. Feeling humiliated and wanting to kill his nemesis, Stewie rigs a lifeguard chair with dynamite and lures Brad beneath it by putting a piece of marzipan under it. However, Stewie's detonator malfunctions, and he blows himself up and is crushed beneath the lifeguard chair. Stewie awakens in Hell. Stewie is abruptly brought back to Earth, and he decides to change his ways.
Meanwhile, Peter gets a job at Quahog 5 News, hosting a ranting segment known as What Really Grinds My Gears, in which he rants about things that bother him, such as Lindsay Lohan and the 19th century. Peter becomes extremely popular, overshadowing Tom Tucker and making him feel jealous. His jealousy causes for himself to get fired.
Stewie's attempts at being a good boy mainly revolve around smothering Brian with affection, much to the latter's consternation. Brian finally goads Stewie into reverting to his old, violent ways, resurrecting Stewie's fear of Hell. Deciding to follow Brian's example of controlling anger through drunkenness, Stewie becomes an alcoholic; Brian, seeking to cure Stewie, takes him out for a night of drinking at The Drunken Clam which culminates in Stewie ramming Brian's car through the wall of the bar.
Knowing Stewie is Peter's son, Tom takes advantage of the situation and presents footage of the accident at the news station. Peter loses his job and Tom regains his post.
The next morning, Stewie wakes up naked in his crib with a hangover, apparently having blacked out and given Roger Moore his phone number the night before. Stewie laments to Brian his lonely existence in the world, and wishes that there were someone else to whom he could relate.
Stu Griffin, as Stewie's future self is called, is taking a time-travel vacation, which is how people in the future take time off. Stewie tricks his way back to the future with Stu. In the future, Stu refers to the younger Stewie as a child named "Pablo" from Nicaragua. Amazingly, no one seems to notice the similarities between the two.
In the year 2035 at a family dinner, Stewie discovers how the lives of his family will pan out: Chris will become a traffic cop and marry a hateful, foul-mouthed hustler named Vanessa who belittles him and insists on putting Peter and Lois in a retirement home; Meg will transition from female to male after college and lives as a man named Ron; and Brian will die by eating chocolate he found in the garbage, go to Heaven, and spend a rather promising eternity drinking with Ernest Hemingway, Vincent van Gogh and Kurt Cobain.
Stewie over time learns of his own horrible fate: at age 35, he will be a virgin working for the Quahog Circuit Shack and living in a low-rent apartment and his only friend will be a female co-worker named Fran. Furthermore, he is a doting mama's boy, having long ago abandoned his matricidal tendencies.
Disgusted with the way his future life will turn out, Stewie remodels Stu's apartment and coaches him through The Joy of Sex with the intent of getting Stu to lose his virginity to Fran. Stu and Fran do end up having sex—for about eight seconds, followed by 40 minutes of Stu crying, and then offering to pay for the sex. Fran goes back to Circuit Shack and tells everyone about it, costing Stu his job. Returning home, he finds that his apartment is in flames, ironically caused by "stress-release" candles Stewie placed while redecorating.
His life now ruined, Stu laments the day of his near-death experience at the Community Pool. Noting that it may be a clue to the reason of his future life, Stewie asks him to elaborate, and Stu reveals that memories of the experience will re-surface when young Stewie is 20, causing him to regress and preventing him from taking any risks. Armed with this knowledge, Stu and Stewie proceed to the retirement home where Lois now resides to ask for money to purchase a new time-travel watch; Lois, who reveals she knew all along that "Pablo" was Stewie, obliges. They buy the watch, but before Stewie leaves Stu realizes that his history will change if Stewie succeeds, and that they will never see each other the same way again. They say their final goodbyes and Stewie begins his mission.
Stewie travels back in time to the day of the accident and runs to the pool. He manages to prevent himself from getting crushed by the chair. Past Stewie wonders what happened and asks Future Stewie who he is - Future Stewie responds, and after a brief talk Past Stewie vaporizes Future Stewie with his raygun. By obliterating Future Stewie, the trajectory of his future is changed, without him knowing. The family packs up and heads home, with Meg bidding farewell to a boy to whom she's been talking to, considering how much she likes his name: Ron.
- Stu & Stewie's Excellent Adventure
- While listing things making him glad, Stewie pronounces the word "pinwheel" as "pinhwheel" as a predecessor to the same error in "Barely Legal".
- Parade Magazine is mentioned when Stu shows Stewie a clipping of a cartoon he cut out of the magazine and stuck behind his counter at Circuit Shack.
- Future Stewie asks past Stewie if there has been a successful vehicle for Ellen Cleghorne. Ellen Cleghorne was a popular black female castmember on the NBC sketch show, Saturday Night Livein the 1990s, who hasn’t been in anything of importance since she left SNL in 1995.
- Stu showing Stewie his prom photo.
- Vanessa’s line about Stewie, “Screw him! That fuckin’ kid’s from Guam!” was shortened to “That kid’s from Guam!”
- Stewie remarking that Stu being fired is “almost as bad as when Peter got fired as the first director of Terms of Endearment,” and the cutaway where Peter zooms in on Debra Winger's chest as she’s telling her children that she doesn’t have long to live.
- Fran's line "I'm putting in my diaphragm" when she's prepping for sex with Stuart was changed to "I'm getting my diaphragm".
- Stewie's line "put your phall-us in her vag-ina" when he's coaching his future self on how to have sex was changed to "put your pen-is in her vag-ina".
- Stewie remembering when Peter got Lois a Galaga arcade cabinet for Christmas.
- Lois requesting of Stewie that, on his way back to the past, he “make sure Chris never marries that bitch Vanessa” and that she never end up in a retirement home, to which Stewie replies by laughing maniacally.