Fox had minor roles in films and television series, including a 1993 episode of the NBC legal drama Law & Order. In 1996, Fox's big break was a recurring role in the NBC medical drama ER, as the no-nonsense vegetarian and lesbian medical intern Dr. Maggie Doyle. She left the show in 1999.

Fox appeared in "The Puppy Episode Part 2", the April 30, 1997 episode of the sitcom Ellen, in which that series' main character came out as gay.

In 1999, she was cast as Secret Service Agent Gina Toscano on the NBC political drama The West Wing, where she starred for one season.

In 2000, she gained a regular role on the CBS police procedural drama CSI: Crime Scene Investigation as Sara Sidle, a Las Vegas forensic scientist.

In 2003, she was ranked #80 in Stuff magazine's list of the 103 sexiest women. She is annually nominated for PETA's "World's Sexiest Vegetarian".

She and CSI co-star George Eads were fired from the show in 2004. Fox had allegedly failed to submit a letter to CBS confirming that she would be on time for shooting. The disputes were resolved in just over a week, and the two were rehired by CBS; however, neither actor's salary was raised, in spite of other cast members' receiving raises. It was also reported that of the two, Fox was approached first to resume her contract with CSI, but she refused until Eads was rehired as well.

Fox is a musician; she plays guitar (badly, she says) and recently purchased a drum kit. She sings and writes songs, most notably the song "Lullabye" for the movie Traveling Companion as well as the song "Satellite," which she published on her official web site. Jorja and CSI co-star Marg Helgenberger sang "Stand by Me" as a duet at the fourth annual benefit called "What A Pair 4—A Celebration of Women's Duets" to benefit breast cancer research at the John Wayne Cancer Institute. It was held Sunday June 11, 2006, at the Wiltern/LG Theatre.

After leaving CSI in 2007, Fox produced the musical Stay Forever: The Life and Music of Dusty Springfield starring Kirsten Holly Smith, about the tension between the public image and private life of bisexual musician Dusty Springfield, which played at the Renberg Theatre in the Los Angeles Gay and Lesbian Center.

After attending the Democratic National Convention in Denver (August 28, 2008), Fox began serving on the Artists & Athletes Alliance Advisory Board and has attended many of their events.

Fox guest-starred in the Lifetime TV series Drop Dead Diva. The episode, which aired on August 16, 2009, had her playing a soccer mom with a Criminal past. She also did a modeling shoot for Green With Glamour. Fox is the co-founder of Honeypot Productions, an independent avant-garde theatre company in Los Angeles that has produced five original plays. Her friend and HoneyPot co-founder Heather Reid wrote Dear Bernard, which Fox helped produce.