Lois' Aunt dies and leaves her the Cherrywood Mansion. The family moves in to the new mansion in Newport only to lose their fortune after Peter makes an extravagant purchase at a charity auction.
Peter's very religious father comes to live with the family after he is forced to retire from his lifelong job at the Mill. Francis, however, is an ultra-religious Catholic who hates Lois and is incredibly intolerant of anyone else. Peter, though, hopes to have the kind of bonding that was missing from his childhood, and when all his plans fail to work out, he resorts to kidnapping the Pope.
Peter, who is concerned that the world is about to end because of Y2K, convinces the family into canceling all their New Year's Eve plans. After bombs destroy everything, the Griffins set off to a Twinkie factory in Natick.
Lois suspects Stewie is the one creating all the pee stains around the house, so she decides to potty-train him. When an incident in the supermarket reveals that Brian is the one responsible, he goes to see a therapist. Brian finds out that his love of Lois is causing his accidents, so he decides to confront her.
When Spooner Street ends up winning the float contest in the Harvest Day parade, a street-wide war breaks out over custody of the trophy. Meanwhile, to raise big money for a new Prada handbag, Meg gets a job at a pancake house, where she pretends that Stewie is her illegitimate crack addicted baby. Child services investigates and soon finds the Griffin home unsuitable for a baby, and take Stewie to a foster home. The residents of Spooner Street declare peace, and decide to rescue Stewie.
When Peter tries to get out of paying a doctors bill by faking his own death, he is visited by Death himself, who wants to take Peter away. After Death twists his ankle while chasing Peter, everyone on Earth becomes immortal while Death is incapacitated.
Lois becomes the director of the production "The King and I" for the Quahog Players theater group. Peters wants to play a role in the production, but becomes more of a nuisance, so Lois decides to make him a producer to get him out of her hair. Peter goes on a power trip and tries to take total control of the play, firing Lois as the director and rewriting the entire play to fit his own vision. The musical is turned into a very interesting, racy cyborg battle.
Forced to go on a womens retreat for telling sexist jokes at work, Peter resists the idea at first. After two weeks, however, Peter becomes a sensitive male. No one likes the new Peter, especially Lois. While attending a charity dinner, Lois does something that snaps Peter out of his feminine phase.
To get a favorite show back on the air, Peter convinces the "Make-A-Dream Come True" Foundation that Chris is dying, and that his wish is for the show to go back on the air. The scam leads to Peter "Magically healing Chris" and people thinking that he is God.
When Lois decides to run for the local school board, Peter runs against her in effort to get his favorite teacher reinstated. Peter and his supporters start a negative campaign against Lois, including a bunch of lies and even sexy pictures of her. Peter's mudslinging works and he is elected. Peter starts some strange policies, including armed robots taking over for hall monitors. The new policies backfire after Chris is caught bringing inappropriate magazines to school. Peter must then think of a way to get Lois back and regain his reputation with the town of Quahog.
Peter runs into a former classmate of his while at the amusement park that the classmate founded. Contemplating his own legacy, Peter starts to think about his future. Chris gives Peter a painting that he painted in order to cheer Peter up, but Peter ends up selling it to a New York art gallery for ,000. Realizing that Chris might be his only hope to have a lasting legacy, Peter pushes Chris to follow his dream of becoming an artist. The family then moves to New York so Chris can become famous.
Meg's slumber party is ruined by her family. She is sick of being embarrassed by them and secretly books the family on a talk show. Intrigued by their story, a network executive gets Peter to sign the family up to be on a reality show. Things quickly go awry, and the Griffins want out of the contract. However, the network owns their namesake, and the family is eventually replaced.
When Brian offers to pick up Stewie from his Grandma and Grandpa's house, they miss their plane back and go on a cross-country journey back home. Meanwhile, Peter and Lois attempt to rekindle their relationship with some marriage videos.
A plane smuggling psychedelic toads from Columbia crashes in Quahog, and toad-licked becomes the new drug of choice in the Quahog high school. Peter infiltrates the high school undercover as a cool kid named Lando Griffin, and is successful in convincing all the kids to quit licking toads. Meg is trying to gain popularity so that a cool kid will ask her to the prom, and decides to go with Peter since he's established himself as an incredibly cool person. However, Peter can't help living out his own fantasies of being the coolest kid in school, and can't say now when the most popular girl in school asks him to the prom, so Peter ditches Meg. Peter and his date are chosen as king and queen of the prom, but Peter is suddenly feeling nothing but guilt. He tells the whole school that Meg broke his heart by dumping him, and makes it look like high school persona was killed after driving his motorcycle over a cliff.
Lois fears that Stewie needs to learn how to be social, so she sends him off to Pre-school, where he falls in love with Janet, a girl who likes his cookies. Meanwhile, Lois becomes a flight attendant, and Peter takes advantage of the free flights.
After the mob helps Peter with destroying his new beat up car, so he can get another new car, he must repay his debt to the mob by taking The Don's nephew, Big Fat Paulie, to the movies. Peter informs Paulie that they can't hang out anymore because of Lois, a misunderstanding that leads Paulie to believe that Peter wants Lois killed.
Due to Brian's embarrassing flea problem, the Griffin's move into a hotel while the house if fumigated. Lois and Peter soon discover that Chris has been skipping gym class because he's self-conscious about his body. Peter tries to talk Chris into getting liposuction, while Lois starts preparing him special low fat meals. Stewie starts taunting Chris by eating everything in sight, and starts packing on the baby fat.
Even though Chris isn't up for surgery, Peter decides to go for it. The new, svelte Peter has Lois all hot and bothered. Peter loves the results of his lipo and decides to have some work done on his face. The new, handsome Peter starts getting all sorts of special treatment: at the gym, at the grocery store, even from total strangers. Lois doesn't like the new Peter's attitude, especially when he joins "The Beautiful People's Club." Karma catches up to Peter while he's on his way to the club. Unable to take his eyes off himself, Peter plunges his car over a cliff. The nasty fall - and subsequent crash-landing into a large vat of lard - leaves him horribly disfigured (ie: back to normal).
The town zoning laws won't allow Peter to build a pool in his yard. When he tries to get a permit, he discovers that his property is actually not part of Quahog, and therefore not part of the United States. Armed with this new information, Peter makes his land his own country, calling it Petoria. When Peter gets no respect in the United Nation, he decides to invade Joe's pool, which brings the U.S. Army to his border. The Griffins can only survive so long without water, electricity, heat, or access to the United States, and finally, Lois and the kids leave President Peter, along with Brian, to his third-world country. Peter finally repatriates only a week after seceding.
After an interview at Brown University, Meg realizes she needs more extra-curricular activities. She joins every club and even tries cheerleading, but fails miserably at them all. Finally, she decides to join the school newspaper.
After many failed stories, Peter fabricates a story regarding actor Luke Perry and uses Meg's byline. Meg and Peter soon become embroiled in a headline-grabbing lawsuit when Luke sues them for defamation of character.
When the local brewery has a contest offering tours of the plant, Peter and his friends go on a drinking binge trying to find the winning beer can. Through a stroke of dumb luck, Peter and Brian actually find one of the winning "scrolls". In a Willy Wonka homage, Peter and Brian start the tour, but are quickly kicked out after drinking the "Beer that wasn't supposed to be tasted."
Meanwhile, Lois's students have a big piano recital/competition coming up - and Lois is praying one of her students wins. She thinks she's got a lock on it when she signs a new student, Ling, a piano prodigy. However, in her enthusiasm, Lois works Ling too hard and she drops out! In an odd twist, Peter - in a drunken stupor over being booted from the contest - sits down at the piano and plays brilliantly! Lois is thrilled and keeps Peter drunk long enough to win the piano recital.
After a father-son camping trip, Peter realizes how irresponsible Chris is after raccoons steal their food and their car. Back at home, Peter gets Chris a job at the local golf course to try and teach him to be more responsible. Chris is content to just pick up golf balls, until he discovers that Peter has entered the father-son golf tournament, with Cleveland Jr.!
Discouraged that Peter is focusing all his attention on Cleveland Jr., Chris rebels by hanging out with Quagmire at strip clubs. Ultimately, Cleveland Jr. abandons Peter, who has an emotional (and deadly) reunion with Chris at the golf course.