The Simpsons' twenty-second season began airing on Fox on September 26, 2010 and ended on May 22, 2011. The Simpsons was renewed for at least two additional seasons during the twentieth season leading up to this season. The cast is currently signed through the 25th season. On November 11, 2010, the series was renewed for a 23rd season by Fox with 22 episodes.
Marge sends Lisa to a performing arts camp, where counselors and fellow campers inspire her to embrace her creative side; upon returning to Springfield, Lisa grows restless with her boring suburban lifestyle.
Lisa invests in Nelson's brand-new business venture, but soon realizes that her friend's instant success might lure him away from the classroom. Worried that his judgment might be clouded, Lisa introduces Nelson to the well-educated and successful creator of Facebook, Mark Zuckerberg, only to find out that he too dropped out of school.
Lisa starts coaching Bart's Little League team; Marge and Bart spend the day at an amusement park, where former MLB manager Mike Scioscia gives Bart advice.
In the 21st Treehouse of Horror episode: Bart and Milhouse discover a real-life board game that they must win to return home in "War and Pieces"; Lisa falls in love with a moody, preteen vampire in the Twilight parody "Tweenlight"; and Marge and Homer go on a honeymoon on a sailboat, and rescue a castaway named Roger who tries to kill them in the Dead Calm parody "Master and Cadaver".
Discovering that Marge was once a stellar A+ student whose grades plummeted after being distracted, Lisa fears that she will end up just like her mom unless she pledges to focus solely on academics in an encore episode. When Marge makes a secret deal allowing Lisa to attend her dream school, Lisa learns a lesson in family and altruism. Meanwhile, Bart puts Nelson Muntz in his place and unintentionally claims the title of "School Bully"
After learning that he is suffering from multiple illnesses and has only a few weeks to live, Mr. Burns becomes distraught by the town’s less-than-sensitive reaction to his announcement. Following an unexpected turn of events, Bart finds Mr. Burns weak and vulnerable in the wilderness and secretly takes him into the Simpsons’ home. But when Homer and Marge learn about their new houseguest, they decide it’s payback time, and Lisa, determined to stand up for Mr. Burns, learns that old habits die hard.
Bart helps nurse an injured pigeon back to health. After Santa's Little Helper eats the bird, Bart has a hard time coping with the loss. Worried that Bart needs some help getting over the loss, Marge and Homer take him to a therapy session with Dr. Thurston, who advises that the only cure for Bart’s blues is to give away the family dog, but when the Simpsons visit the pup’s new home, a shock causes them to rethink their decision.
When the rest of the family seems to lack Christmas spirit, Marge contacts Martha Clause (Martha Stewart).
Jon Hamm will guest star as a Federal Bureau of Investigation agent as Homer goes undercover to infiltrate Fat Tony's mob. Joe Mantegna will return as Fat Tony, and also voice his cousin Fit Tony.
Marge reconnects with a close group of mothers she used to be friends with; Bart tries to break up their group when his playdates stop being fun.
When Smithers transforms Moe's pub into a refined and trendy lounge, the establishment becomes Springfield's local gay hangout; Principal Skinner falls for the new, free-spirited music teacher (Kristen Wiig).
When Homer insists Bart must earn the new dirt bike he wants, Bart comes up with a scheme; James Lipton interviews a TV cast.
Moe gets Homer to be his wingman, but becomes distraught when the women are drawn to Homer as well. Meanwhile, Marge discovers some gray hairs and tries a new more mature hair style to go along with it, much to Bart's dismay.
Bart and Homer make a film based on Bart's comic book character Angry Dad. The cartoon becomes a critical favorite and begins to win a number of awards, but Bart becomes upset when Homer takes all of the credit during acceptance speeches.
After a field trip to the desert, Lisa discovers that the desert water mysteriously makes typically combative creatures get along, so she brings some of the water home as a souvenir. When Grampa moves in with the family after getting kicked out of the retirement home, Homer secretly tests the desert water on Grampa, who is instantly cured of his crankiness. A pharmaceutical representative (guest voice Herzog) gets word of Homer’s discovery and quickly tries to replicate the water into a drug, using Grampa as the primary guinea pig. But when the pills get in the wrong hands and are sold on the black market, unexpected side effects of the new drug take an eye-popping toll on the elderly citizens of Springfield, and the Simpsons learn that their new medical cure comes with major consequences
The town is abuzz when Cheech and Chong announce a Springfield stop on their much-anticipated reunion tour. But when Cheech and Chong take the stage in front of their loyal fans, the jokes were just not the same for Chong, so Homer steps in and delivers all the punchlines by heart. Impressed, Cheech invites Homer to go on tour with him as new duo “Cheech and Chunk” while Chong forms a more progressive comedic team, “Teach and Chong,” with Principal Skinner. While Homer is on tour, Marge attempts to help the neighborhood cat lady and change her hoarder ways, but turns into a hoarder herself in the process, and Homer realizes that life on the road is not all high times and slapstick humor
When Homer inadvertently humiliates Bart in front of a stadium crowd, Marge encourages Homer to enroll in a fathering enrichment class taught by therapist Dr. Zander (guest voice Rudd). Shocked to learn that Homer often strangles Bart for mischievous behavior, Dr. Zander conducts a series of treatments with the help of Kareem Abdul-Jabbar (guest-voicing as himself) to teach Homer what it feels like to be young and small. But when Bart learns that the therapy sessions have transformed Homer into a pushover, he takes advantage of Homer and becomes a school bully. Hoping therapy could also cure Bart of his bullying habits, Marge enlists Dr. Zander’s help to patch their relationship
The family is greeted by folk singer Ewell Freestone (guest voice McBrayer) when they visit a peach farm, but when Marge goes overboard with peach-inspired dishes, Lisa and Bart try to get rid of the unwanted fruit. Later, Lisa becomes a magician’s apprentice to the legendary Great Raymondo (guest voice Landau) who helps her develop her craft, but a schoolgirl crush clouds her judgment when she is coaxed into revealing the Great Raymondo’s most famous magic trick to his phony archnemesis. But when the rival magician’s act takes a risky turn, the Great Raymondo has one last trick up his sleeve and stages showdown with Ricky Jay, Penn & Teller and David Copperfield (guest-voicing as themselves), showing them why he is the master of the craft
Fat Tony (voice of Joe Mantegna) woos Marge's sister Selma, and they marry. Marge worries that Selma is choosing her new lifestyle over family after the whirlwind romance, but Tony invites Homer and Marge to join them on a getaway at the Jersey shore. Meanwhile, Bart develops a gift for finding truffles, much to Lisa's delight.
After Homer discovers a genius talent for styling hair and opens his own salon, he becomes Springfield’s most in-demand hair stylist. But having to listen to women’s problems and gossip all day long leads Homer to believe his gift may actually be a curse. Meanwhile, when Milhouse decides to live each day to the fullest, he comes out of his shell and professes his love for Lisa, only to have his heart broken. Milhouse then catches the eye of popular fifth-grader Taffy, causing Lisa to make a bold move.
When the Simpsons discover a collection of keys to every door in Springfield, Lisa stumbles upon an eerie hidden classroom beneath Springfield Elementary School. When she shares her discovery with Principal Skinner, the secret room mysteriously disappears and he takes the only key away. A determined Lisa uses her detective skills to lead her back to the room to solve an old school mystery.
Feeling guilty for getting Mrs. Krabappel suspended after one of his school pranks, Bart helps her escape detention, and Ned Flanders winds up saving her life in the process. When Edna and Ned start dating, he is surprised to learn she's been with many of Springfield's men, including Homer and Aerosmith drummer Joey Kramer.