During a benefit concert in Paris, France, David Seville is injured from a backstage accident. Having to recuperate there, Dave asks his aunt Jackie to look after the Chipmunks, Alvin, Simon and Theodore. Arrangements are also made for them to go to school at West Eastman High School. After Jackie also causes an accident, the Chipmunks are left in the care of Toby, Jackie’s grandson.
Meanwhile, Ian Hawke lives in the basement of JETT Records. Three singing female chipmunks, Brittany, Jeanette, and Eleanor, also known as The Chipettes, emerge from a FedEx package and Ian hires them as plot to get back at the Chipmunks and revive his career.
While at school, the Chipmunks are ridiculed by jocks, who threaten to kill them for drawing their girls’ attention away from them. They chase the Chipmunks around the school and try to drown Simon in a toilet. They visit the principal’s office, only to discover that the principal, Dr. Rubin is a huge fan, and enlists their help to raise money for a music program by participating in a contest. Meanwhile, Ian is shocked to find the Chipmunks on the front page of his newspaper. After he reads a story about them, he quickly sends the Chipettes to school.
When the Chipmunks meet the Chipettes, a rivalry forms after the former group learns that the latter group are with Ian. Meanwhile, Alvin becomes popular with the jocks and joins the football team, not realizing that the next game is during the concert. At the concert, Theodore and Simon tell the fans that Alvin did not show up and that they cannot perform, leading to a victory for the Chipettes. When Alvin finally shows up after the concert is over, he finds the auditorium empty, Brittany calls him out for lacking responsibility and is ignored by his brothers at home.
Soon the Chipettes are hired, but learn that the concert they are to perform as an opening act for a Britney Spears concert at the Staples Center is on the same night as the school contest. Ian convinces them to blow off the battle and perform at the concert, but refuses to give the same credit to Jeanette and Eleanor that he gives Brittany. She demands that they all perform together or not at all, until Ian threatens to send them to a barbecue restaurant unless they perform.
Before the Battle Of The Bands, Alvin receives a call from the Chipettes who tell him that Ian has locked them in a cage, so Alvin races off to rescue them while Simon tells Jeanette how to open the cage over the cell phone. Simon and Theodore are on the verge of going out to perform until the others arrive just in time to perform at the contest. The Chipmunks and the Chipettes perform together and receive the money for the music program. Dave, who had left the hospital upon learning that Toby was looking after the Chipmunks, returns during the contest happy to see his boys again. Meanwhile, Ian gets into more trouble at the concert of Staples Center he set up for the girls when he attempts to imitate them only to be taken away by the security guards. After the contest, Dave allows the Chipettes to stay with them.
In the mid-credits, Dr. Rubin has the jocks scrape the gum off from under the bleachers in the gymnasium. In the post-credits, Ian is thrown into a dumpster.