Alvin, Simon and Theodore (featuring the modified voices of JUSTIN LONG, MATTHEW GRAY GUBLER and JESSE McCARTNEY, respectively) have their lives thrown for a loop when their manager and legal guardian, Dave (JASON LEE), is injured during a concert in Paris. The three rodent brothers then fly back to Los Angeles where they are to be cared for by Dave's ne'er-do-well cousin, Toby (ZACHARY LEVI).
Acting on Dave's wishes to have the three chipmunk pop-stars live as normal a life as possible, Toby enrolls them at the local high school where they quickly draw the attention of the principal (a closet Chipmunks fan played by WENDIE MALICK) and the school bully (KEVIN G. SCHMIDT).
At the same time, their disgraced and still-unscrupulous former manager, Ian (DAVID CROSS), looks to get revenge on the chipmunks by discovering and then promoting a female version of the band, dubbed the Chipettes (voiced by CHRISTINA APPLEGATE, ANNA FARIS and AMY POEHLER). When Alvin becomes the school's newest sports star, Simon and Theodore are left to fend for themselves, leaving the band's future in jeopardy.