Peter and Lois decide to go on a second honeymoon. But when Peter crashes the car, he decides to pose as Mel Gibson to stay in his fancy hotel suite, where they find a copy of a "The Passion of the Christ" sequel. They attempt to destroy the film and end up being chased by two priests who went to retrieve the film.
Brian becomes a substitute teacher at Chris' school after his teacher wins the lottery. When Brian is moved to teach a class of troubled kids, Chris falls in love with his new teacher, Mrs. Lockhart, who promises to love Chris only if he kills her husband. When Lois finds out, she and Stewie decide to teach Chris a lesson.
After Mort bowls a perfect game, and Quagmire gets a key to the city by performing CPR, Peter notices he has nothing to be proud of. He then attempts to achieve fame by setting the world's record for most nickels swallowed. However, a slight miscalculation leaves him blind with nickel poisoning.
When Meg gets turned down for a date, she asks her family for support. Lois ends up taking her to the mall, where she gets the ultimate makeover. Meanwhile, Peter tries to start a band with the guys, but when their first gig fails, the family ends up performing. Impressed by Meg's singing, a record producer signs the family, and their travels eventually land them on "Saturday Night Live."
When Peter hears Loretta scream, he tries to help out, but discovers Loretta is cheating on Cleveland. Peter figures out that it was Quagmire and decides to tell Cleveland about it. But when Loretta walks out on Cleveland he doesn't take it lightly.
After winning a game of Trivial Pursuit, Peter is convinced he is a genius. To prove Peter wrong, Brian suggests he take a test of the MacArthur Genius Grant. The test results say that Peter is technically mentally challenged. Peter has no problem abusing this handicap until Lois is injured and the kids are taken away because Peter is not mentally fit for parenting.
"The Bachelorette" comes to Quahog and Brian is chosen to be a contestant. Brian does not like the show, but participates just to have a vacation only to wind up falling in love with the bachelorette. Meanwhile, Chris gets a nasty pimple on his cheek, which talks to Chris and likes to cause mischief.
Peter runs up his tab at Morts Pharmacy. When he is told he has to pay, he decides to sell Meg to the Goldmans, who gives Meg to Neil. When Meg finds out that Neil is dating another girl, she becomes jealous and tries to find herself a boyfriend. Meanwhile, Stewie falls in love with Liddane, his new babysitter.
Lois's kleptomania lands her in jail, leaving the Griffin household in a worse state of disarray than usual. In an effort to restore their lives Peter breaks Lois out of jail, only to find themselves fugitives living in "Asian Town" Peter takes up sumo wrestling to pay the bills, until Joe sees Peter on television and goes after them. The family takes refuge in the sewers but it is no use; Joe follows them even down there. A miscalculation sends him hurtling towards his certain doom when Lois saves him... which somehow magically absolves her of her crimes.
Lois fulfills a lifelong dream of being a model. Stewie starts on a multi-level marketing company. Brian in need of cash to buy his de-worming medication agrees to become his salesman.
Peter and Brians friendship becomes strained after Brian begins dating Megs high school teacher. Peter finds a replacement in new best friend James Woods, who is visiting Quahog because of a suggestion to rename James Woods High School after Martin Luther King Jr.
When Peter and the guys decide to go fishing, they end up caught in a storm. Stranded on a desert island, their families fear the worst. Rescued by a cruise ship months later, Peter suprises Lois at home, where he finds out that she has a new husband.
When Chris is supposed to be hazed for a school tradition, he runs off to South America; Peter quickly becomes frustrated by his new job at the beer factory.
After a "wardrobe malfunction" occurs during a live broadcast, the FCC begins to censor all of Peters favorite television shows. As a result Peter creates his own TV station PTV which broadcasts from of the Griffin home. Peter and Brian create their own edgy programming for the station until the FCC shows up to shut down PTV, and censor all controversial material in Quahog.
After writing a story for a local magazine, Brian gets a job at The New Yorker. He admitted that he didn't graduate from college and lost his job. So he went back to college. In the end, he failed.
Lois thinks Stewie is trying to kill her due to his lack of quality time with his father, so she orders Peter to spend more time with Stewie. Meanwhile Chris starts a friendship with Herbert.
Lois discovers she has a brother named Patrick and therefore takes the family cross-country to meet him. However, it turns out that he's in a mental institution, but Lois thinks he's sane, so she checks him out to live with the Griffins. Meanwhile, Peter starts a Society for the Acceptance of Fat Men. However, the fat men of Quahog are strangled one-by-one.so the Fat Society live in terror. Who is the strangler?
When Peters dad visits the family, he tries to impose his religious beliefs on the family. But after a mixup with holy-water leaves Stewie in a bubble, Peter decides to form a church around his hero, The Fonz.
After Brian has a near-death experience in the hospital, he decides to lead a new life. He ends up getting a nightly singing gig with Frank Sinatra Jr., but his new lifestyle doesn't last very long. Meanwhile, Meg, after joining a new after-school group, pretends to be a lesbian.
At his high school reunion, Peter tries to impress his fellow classmates. When Peter, heading for the bathroom, charges through the crowd of people, he impresses quarterback Tom Brady, who offers Peter a spot on the New England Patriots. Meanwhile, Brian owes Stewie money, after Stewie becomes a sports bookie.
When Peter wins a maid for a week as a prize on a game show, Quagmire gains an interest in her, and they eventually marry. Quagmire, stricken with his bachelor ways, tries to get out of the marriage. Meanwhile, Lois stops breast-feeding Stewie, who, as a result, goes through withdrawals.
Peter gets a vasectomy and loses all his sex drive. Lois begins to gain weight, and as a result, Peter's regains his interest in his wife. When Lois' habits get out of control, she has a heart attack. The surgeon must remove Lois' fat to reach her heart, returning her to her normal weight. Meanwhile, Stewie's half-brother Bertram returns to confront him, where they have a war for control over the playground.
Meg becomes an intern for Mayor West. Brian, who is sure that the mayor is corrupt, tries to out him. Brian and Stewie, while undercover, discover that Meg is more than just an intern. Meanwhile, Peter and Lois go back to their folk singing days at a local talent show. When they begin using drugs, Chris stages an intervention.
After reading an erotic novel, Peter gets the idea to write one himself. Carter gets sued for publishing Peter's book on tape and loses all his money, where he is forced to become a middle-class citizen. Meanwhile, Stewie tries to train for the Olympics.
Brian's gay cousin Jasper visits the Griffin house and announces that he is engaged to his partner and wants to be married at their house. When Mayor West bans gay marriage in an effort to cover up and bring attention away from a scandal of his own, Brian resorts to hostile actions to try to change the Mayor's mind. Lois and Peter question their view towards gay marriage while Chris joins the "Young Republicans" Club to impress a girl.
Peter wants to top Joe, who just built a new home theater system, so he starts to build a multiplex in his backyard. In doing so, he discovers an Indian burial ground. He finds an Indian chief's skull and the Griffin house becomes haunted. Stewie gets sucked into the television and strange events follow as they try to get Stewie back from the poltergeist.
After robbers enter into the Griffin house, the family tries to gain safety in Peter's panic room. Trapped with no way out, Peter decides to tell his family the history of their ancestry by narrating a chain of events that describe his family's past.