Brian Fairlee giving an episode preview was phased out and replaced with the return of the cold opening sketches (mostly music video parodies, fake commercials, mock movie trailers, and TV show promos).

Notable celebrity appearances this season (besides the ones from the clip show episodes) include: Carlos Mencia, Neil Patrick Harris, Dave Navarro, John Reep, Kathy Griffin, Serena Williams, and former MADtv cast members Debra Wilson and Mo Collins.

Sketches include: "UPS: Brown Innuendo" fake commercial, "Flashlight Masturbators", "The Zapruder Home Movies", "Wizard of Oz Deleted Scene: The One-Legged Slave", "Mary Poppins Deleted Scene: Illegal Mexican Housekeepers"; the music video parody of Nelly's "Hot in Herre" about pedophilic Catholic priests, "RU-486: Motherly Regrets" fake commercial, "Ace Hardware: John Madden's Birdhouse Injuries", "Sesame Street: Big Bird Gets the Bird Flu", "Closeted Gay Football Fans", and "Brain's Scented Farts".NOTE: This episode also mentions a banned sketch called "Schindler's Lost" that was originally supposed to air during the show's first season, but was pulled for being too offensive.

Music video parody of Rihanna's "Umbrella" has Hillary Clinton (Parker) madly in love with Barack Obama (Key); new feature player Dan Oster reads a snippet of a romance novel he wrote himself; Coach Hines fields questions from students; promo for a new cable channel dedicated to "dangerous job" reality shows in the same vein as The Deadliest Catch and Ice Road Truckers; a deleted scene reel from Kathy Griffin: My Life on the D-List; AT&T now has service for people in suggestively-named towns; another installment of Johnny Sanchez and Bobby Lee's Rice And Beans: The Heartland Tour; Bon Qui Qui (Johnson) annoys her customers at King Burger; a couple (McDonald, Parker) try to explain themselves to a police officer (Key) over a speeding charge; Jon Reep does stand-up.

Parody of Avril Lavigne's music video "Girlfriend" has L'il Mama (Hall) teaming up with Lavigne (Myrin) to give her street cred and save her from being sued for using Toni Basil's "Mickey" in her new song; Bobby Lee does motion capture for a fantasy video game; claymation auditions for fight scenes and love scenes; an unseen viewer switches between a Spanish variety show and news of a meteor on a collision course with Earth; Prison Break promo exposes the show's repetitive storyline; a black poet (Hall) uses spoken word to call out her ex-boyfriend (Peele); 24 parody where Jack Bauer (Oster) uses his brutal interrogation skills on an old man, an orangutan, and a little boy; parody of Criss Angel's Mindfreak has Flava Flav (Peele) ruining Criss Angel's (McDonald) tricks.

A spoof of BBC news featuring a parade of ugly British anchors; parody of crime drama Women's Murder Club where the women act too stereotypically feminine to get any work done; claymation sketches for monster and superhero auditions; Bobby Lee stars in his own survival reality show; a husband (Peele) thinks his wife (Flanagan) hired a teenage babysitter (Myrin) to come over for a threesome; a black man (Key) with a spot-on Bill Cobsy impression gets upstaged by a white man (Oster) with a better one; Bobby Lee and Johnny Sanchez continue their Rice And Beans tour; a convenience store clerk (Sanchez) thinks one of his customers (Key) is a Muslim.

Juno sequel has quirky teen (Flanagan) harvesting organs; Barack Obama (Key) and Oprah (Hall) sing about how the former beat Hillary Clinton in the polls; in a thinly-veiled parody of the Eliot Spitzer scandal, press conference reporters criticize a deposed governor's (McDonald) cuckolded wife (Flanagan) for being oblivious to his infidelity and sexual misconduct; Fun With Clip Art shows a depressingly awkward conversation between bicyclists; Celebrity Rehab with Dr. Drew features burnt-out D-list celebs and a bad performance of "Greased Lightning"; Hilarry Clinton (Parker) gets a ride from The Depressed Persian Tow Truck Man (McDonald); Bobby Lee and Arden Myrin go to an American Idol party; a white shopper (Parker) can't describe a saleswoman who disappeared without bringing up the fact that the missing saleswoman was black; a depressed self-help author (Flanagan) speaks at a women's empowerment seminar; Roger Clemens' (Oster) interview about his steroid abuse is filled with innuendo about "getting fingered".

Spoof of the FreeCreditReport.com commercials has the singing spokesman (Oster) in jail and homeless after not paying off his credit cards; Dr. Phil (McDonald) tricks Britney Spears (Parker) and her family (Flanagan, Myrin, and Oster) into appearing on his show; on the latest installment of 24 with Bobby Lee: Dave Navarro discovers that Bobby Lee has a boil he got from lying to a blind girl; new movie Spin Up centers on sign spinners preparing for a dance-off; Sesame Street parody shows the fun side to living on the brink of economic collapse; Coach Hines (Key) returns to teach his class the art of war while on a paintball course; Luann Lockhart (Flanagan) does stand-up; the notorious Grand Theft Auto video game series is now a board game the whole family can play; in a send-up of American Idol, Bobby Lee and an old man are chosen as finalists over who will stay on MADtv as a cast member; a "Feed the Children" commercial parody has the announcer promising stronger kids with more donations.