Cox was born in Los Angeles, California, the daughter of Meredith and Terry Cox, who is a personal manager. She has one younger brother, Matthew Cox, who is also an actor. She began her career at the age of four when she appeared as a dancer in several ballet productions and TV specials. She began acting at the age of ten, making appearances in several movies and guest starring on shows such as Baywatch, Star Trek: The Next Generation, Eerie, Indiana, and Blossom. She also starred in General Hospital from 1993 to 1995 and had a recurring role on the Saturday morning program California Dreams.

Her appearances on various TV shows led to her first prime-time starring role as Tiffany Malloy on the sitcom Unhappily Ever After, which ran on the WB 1995–1999. Her brother Matthew guest-starred on a handful of UEA episodes, including one where he wore a "Ghostface" mask (à la Scream).

When Unhappily left the airwaves after taping 100 episodes, Cox went on to portray former prostitute Taylor Clayton on the sitcom The Norm Show and star as Nikki White in Nikki, a sitcom vehicle that lasted for less than two seasons (2000–2002). She starred as Mary Connell on the TV drama Las Vegas from 2003-2007. On May 20 and May 23, 2005, her Las Vegas character crossed over to NBC's soap opera Passions to coincide with the arrival of two new characters introduced on Las Vegas.

After being romantically linked to Kevin Connolly, who played her brother on Unhappily Ever After, Cox was engaged in 1999 to Bobcat Goldthwait.

On December 29, 2006, she married comedian/actor Jay Mohr in Los Angeles. In December 2008, Jay petitioned a Los Angeles court to allow him to legally add Nikki's last name to his, changing his name to Jay Ferguson Cox Mohr.

James Caan · Nikki Cox · Josh Duhamel · James Lesure · Vanessa Marcil · Tom Selleck · Molly Sims · Marsha Thomason