Having grown up unwanted in an orphanage until she blossomed into a sexy young woman, Shelley Darlingson (ANNA FARIS) lives a blissful, if seemingly dimwitted life in the Playboy mansion, dreaming of one day being named a Playmate centerfold. That dream is unexpectedly shattered, however, when she receives a letter -- supposedly from Playboy founder Hugh Hefner (HUGH HEFNER) - informing her that she's being kicked out. She can't believe it, especially since she just turned 27, but as her mansion bartender friend Marvin (OWEN BENJAMIN) informs her, that's the equivalent of 59 in bunny years.
After a misunderstanding briefly lands her in jail, Shelley happens across the local university where she walks in -- scantly clad -- on a meeting of sorority house-mothers. While the likes of Phi Iota Mu house-mother Mrs. Hagstrom (BEVERLY D'ANGELO) looks down her nose at the former bunny, another informs Shelley that the Zeta Alpha Zeta house is in search of a new matron.
They're the decidedly less than cool or popular sorority with just seven members who are facing their charter being revoked by Dean Simmons (CHRISTOPHER McDONALD) if they can't attract 30 new pledges. And that seems unlikely, what with unofficial leader Natalie (EMMA STONE) coming across as nerdy; Idaho farm girl Carrie Mae (DANA GOODMAN) appearing a bit too masculine; Harmony (KATHARINE McPHEE) being quite pregnant; multi-pierced Mona (KAT DENNINGS) always sporting a sarcastic scowl; Joanne (RUMER WILLIS) wearing a full upper body brace; Tanya (KIMBERLY MAKKOUK) making little to no impression; and Lily (KIELY WILLIAMS) living in the closet and only communicating through text messages.
With Shelley needing a place to live and Natalie thinking this new addition might be able to draw boys and thus new pledges to their sorority, the former bunny moves in as their new house mother and immediately sets out to give the girls a makeover in hopes of helping them be more attractive to the guys, such as Colby (TYSON RITTER) for whom Natalie has a secret crush.
Yet, as that transformation begins and Shelley finds herself attracted to nursing home manager Oliver (COLIN HANKS), they must contend with Mrs. Hagstrom and the girls of Phi Iota Mu, including Ashley (SARAH WRIGHT), who want to undermine their efforts so that the Zeta charter is rescinded and they can take over their house.