Ross Bagdasarian Jr. dreamed of making a live-action Chipmunks film since 1997, but the project went through many troubled iterations, describing the process as having 'many nightmare moments'.

In 1997, Robert Zemeckis was originally set to direct a live-action adaptation produced by Steven Spielberg for Universal Pictures, but the project was shelved after Bagdasarian Sr.'s estate sued Universal in 2000 over licensing issues.

Many well-known actors were considered for the role of David Seville before Jason Lee was cast, including Chevy Chase, Tim Allen, John Travolta, Ben Stiller, Adam Sandler, Jim Carrey, and Bill Murray.

Patton Oswalt and Brian Posehn were both approached to play Ian Hawke and declined before David Cross took the role; Oswalt later joked that he and Posehn threw the script across the room and 'David Cross caught it,' prompting Cross to publicly explain he had actually reconsidered after initially rejecting the part.

The three chipmunk voice actors—Justin Long, Matthew Gray Gubler, and Jesse McCartney—replaced Ross Bagdasarian Jr. and his wife Janice Karman, who had voiced the characters since reviving the franchise; the new actors recorded their lines slowly so they could be sped up in post-production, a process Jesse McCartney called 'tedious,' sometimes requiring up to 40 takes per line.

Dave Seville's house set, built at Sunset Gower Studios, contained hidden tributes to creator Ross Bagdasarian Sr., including his actual piano, a flower he painted, an address number incorporating 1958 (the year he created the Chipmunks), and a design based on a cottage built in 1919 (his birth year).

To help actors interact convincingly with the CGI chipmunks, they rehearsed scenes using small stuffed animals to mark the chipmunks' positions, then performed the actual takes from memory after the stand-ins were removed.

For the mid-credits scene where Ian tries to get squirrels to sing, the actor and the real squirrels were filmed separately, with a trainer using nuts to bait the squirrels into turning their heads in different directions.

Rhythm & Hues Studios, the visual effects company behind the chipmunks' animation, had previously won an Academy Award for The Chronicles of Narnia: The Lion, the Witch and the Wardrobe and used its own proprietary software, along with programs like Voodoo, Icy, Flame, and Maya, to integrate the CGI chipmunks into live-action footage.

It took Rhythm & Hues until September 2006 to finalize a look for the chipmunks that felt realistic for live action while still keeping the essence of their classic cartoon design, studying real chipmunks as well as every past version of the characters.

Animators referenced human dancers to animate the chipmunks' dance movements and studied YouTube videos of famous guitarists to realistically animate Alvin's guitar playing.

Despite widespread predictions from film bloggers that it would flop due to the involvement of the Garfield: A Tail of Two Kitties director and writers behind poorly received comedies, the film grossed $365 million worldwide against a budget of just $55–60 million, surprising even the studio.

Fox submitted the film for Best Animated Feature consideration at the Academy Awards before it had completed the theatrical run required for eligibility, and it was not nominated.

The film's home media release sold 7.5 million DVD units generating $127.6 million, making it the third-best-selling DVD of 2008 in the United States behind only The Dark Knight and Iron Man.