His first notable work was with Ten Hands, a locally popular Denton, Texas band. Ten Hands briefly enjoyed heaps of acclaim and an impressive following in the band's home state. In 1988, Chamberlain left Ten Hands to join Edie Brickell & New Bohemians, with whom he toured and recorded from 1988 until 1991 when the band broke up. He can be heard playing on the band's 1990 album, Ghost of a Dog. In the summer of 1991, he briefly joined the band Pearl Jam and toured with the band before the release of its debut album, Ten. He can be seen in the band's first video, "Alive". Chamberlain said, "I toured in the van with them, played a bunch of clubs—I had a good time, definitely had a good time. They wanted me to join the band, but Edie Brickell & New Bohemians had just broke up, I had just got off the road after touring for four years straight—I could not imagine doing it again." For his replacement, Chamberlain suggested drummer and friend Dave Abbruzzese. Chamberlain left Pearl Jam to join the house band for Saturday Night Live during the 1991-1992 season where he was able to play with and back up artists such as Johnny Winter, Charlie Musselwhite, Jon Faddis, Steve Turre, Leon Pendarvis and work with comedians Steve Martin, Chris Farley, Mike Meyers and Dana Carvey on musical skits.
At the end of 1992, he moved to Seattle, Washington to start the band Critters Buggin with Skerik and Brad Houser. The band has since released six albums and is currently active. In 1993, Chamberlain toured as a member of the funkband Weapon of Choice. In 1996, he received career boosts after performing on albums by The Wallflowers (Bringing Down the Horse) which he won a Grammy for "best recorded performance" and Fiona Apple (Tidal). In 1998, Chamberlain began working with singer-songwriter Tori Amos, with whom he gained recognition. He performed on her 1998 album, From the Choirgirl Hotel, and since then he has contributed to several of Amos' albums and tours. He has worked on combining live and looped drums, often creating loops on the fly and then playing along to them. Amos has introduced Chamberlain as "the human loop" at her concerts. He was nominated Musician Of The Year at the 2004 CMA's.
Since the mid-1990s, Chamberlain has become well known as a session drummer, having appeared on over 200 records with sales well over 80 million worldwide. The diverse range of artists that Chamberlain has contributed his drumming to the tours and albums of include Peter Gabriel, The Wallflowers, Fiona Apple, Sam Phillips, Kanye West, Weapon of Choice, David Torn, Tori Amos, Chris Isaak, Macy Gray, Stevie Nicks, Dave Navarro, Kevin Max, Master Musicians of Jajouka, Stone Gossard, Martina McBride, Garbage, Elton John, Natalie Merchant, Anika Moa, David Bowie, Brad Mehldau, Keith Urban, Liz Phair, John Mayer, Finn Brothers, William Shatner, Jon Brion, Robbie Williams,Shakira, Morrissey, Indigo Girls, Sean Lennon, Sarah McLachlan, Sara Bareilles, Brandi Carlile, Dido, Lisa Marie Presley, Elvis Costello, Bruce Hornsby, and Regina Spektor.
In 2005, he released a self-titled solo album on Web of Mimicry Records that he describes as "an imaginary soundtrack to an Asian-Western-Sci-Fi-Horror Movie." He is in a group called the Slow Music Project with Bill Rieflin, Peter Buck, Robert Fripp, Hector Zazou, and Fred Chalenor. In August 2007, Chamberlain and musician Bill Frisell released the debut album for the musical project Floratone. In 2010 Drum Magazine named him one of the 15 Greatest Groove Drummers Of All Time.
In 2011 he started a solo Electro/Acoustic project called "Company 23" He will be releasing a recording for this project and doing shows in 2011.