Dave Seville (JASON LEE) is a marketing man who dreams of being a songwriter. Accordingly, he's always approaching his college friend, Ian Hawke (DAVID CROSS) of Jett Records, with his latest work, but none of that ever flies. Throw in a failed romance with ex-girlfriend Claire (CAMERON RICHARDSON), and things couldn't seem to get any worse for the young man.
Yet, he seems to think they have when he suddenly finds himself in the company of three chipmunks that have suddenly inhabited his house, making a mess of the place. Much to his surprise, however, Alvin (voice of JUSTIN LONG), Simon (voice of MATTHEW GRAY GUBLER) and younger sibling Theodore (JESSE McCARTNEY) not only can talk, but they can also sing in perfect, albeit high-pitched harmony.
It's not long before the chipmunks are belting out the songs Dave is writing for them, and they're soon a big hit on Ian's label. Despite not being the sort one would deem a family man, Dave tries to care for his young charges, but hampers their fun in the process. Sensing his opportunity to pounce, Ian makes Dave out to be the bad guy and convinces the chipmunks to come and live with him.
As he puts his marketing efforts into hyper drive and pushes the talented rodents toward exhaustion, however, they and Dave wonder if the wrong decisions were made and whether they'll make wonderful music together ever again.