A tree that the chipmunks Alvin (Justin Long), Simon (Matthew Gray Gubler) and Theodore (Jesse McCartney) live in is cut down and driven to Los Angeles. Once in L.A., the Chipmunks meet struggling songwriter and composer David Seville (Jason Lee) who had his latest song rejected by JETT Records executive Ian Hawke (David Cross), his old college roommate. Dave also once had a relationship with his next door neighbor, Claire Wilson (Cameron Richardson).
After winding up at Dave’s interview, the Chipmunks hop into a basket Dave stole from one of Ian’s coworkers and follow him home. Once there, Dave discovers the Chipmunks and kicks them out, only to hear them sing “Only You (And You Alone)”. Dave then makes a deal with them; they sing the songs he writes, and he provides food and shelter for them. Unfortunately, when Dave tries to present the Chipmunks to Ian, they fail to sing to him on account of stage fright. Making matters worse, Dave is dismissed as the chipmunks ruin his job presentation by coloring on it. When Alvin tries to set the mood for Dave’s dinner with Claire, things become peculiar and she rejects Dave after having been told about the Chipmunks. To make it up to Dave, the Chipmunks go to Ian in an attempt to get a record deal.
Once the Chipmunks sing Dave’s song to Ian, Ian signs them to the label and calls Dave the next day. After a few singles, the Chipmunks have a worldwide success. When Dave expresses concern for their well-being and insists that the Chipmunks are “children” who do not need so much craziness in their lives, Ian convinces the Chipmunks that Dave is holding them back. After a misunderstanding with Dave, they go live with Ian. They become enchanted with Ian at first, but once they set off on a nationwide coast-to-coast tour, Ian takes advantage of their naïvete, changing their image and working them constantly. Meanwhile, Dave misses the chipmunks and he wishes they would come back home. He calls Ian to see if he can talk to them but Ian refuses, and then conceals Dave’s motives from the boys. Later, the Chipmunks are wearing out, and it is all over the news. Angered by what Ian has done to the three, Dave decides to take matters into his own hands by infiltrating their concert.