Ribisi, who is Sicilian-American, was born in Los Angeles, California to Gay Landrum, a talent agent, and Albert Ribisi, a musician. He is the twin brother of actress Marissa Ribisi, and has another sister, Gina.

Ribisi began his career in network television with recurring and guest roles on a number of shows, including The Wonder Years and My Two Dads. He entered the public eye with a prominent performance in The X-Files episode "D.P.O.," as well as with his recurring role as Frank Jr., the brother of Phoebe Buffay (Lisa Kudrow) on Friends. More recently, he has appeared in four episodes of My Name Is Earl, earning a 2007 Emmy nomination for his performance on the series. His film credits include Saving Private Ryan, That Thing You Do!, Boiler Room, subUrbia, The Gift, Basic, Lost in Translation, Flight of the Phoenix and Sky Captain and the World of Tomorrow.

Ribisi has also appeared on the video of British band Keane's single Crystal Ball, which was released worldwide on August 21, 2006. He also appeared with Winona Ryder and John C. Reilly in a Jon Spencer Blues Explosion music video.

Ribisi was married to Mariah O'Brien from March 18, 1997 through November 3, 2001; the couple had a daughter, Lucia, born in December 1997 and named after the doomed heroine in the Donizetti opera, Lucia di Lammermoor. His twin sister, Marissa, is also a Scientologist and is married to Scientologist indie-rocker Beck.