Gayheart was born in Hazard, Kentucky and raised in nearby Pinetop (also in Kentucky) by parents of Irish, Italian, German and Cherokee Indian heritage. She is a coal miner's daughter. She moved to New York City at 15 where she completed her education at New York's Professional Children's School and the Lee Strasberg Institute and began a career acting and modeling. Her major break was a series of television commercials for Noxzema in the early 1990s, earning her the moniker "The Noxzema Girl."

Gayheart plead no contest to misdemeanor charge of involuntary vehicular manslaughter following a 2001 incident where she struck a nine-year-old boy crossing the street in Los Angeles. Although the boy was jaywalking, traffic had stopped to let him pass. Gayheart allegedly swerved into a left-turn-only lane to pass the stopped cars and struck the boy, who died the following day from his injuries. Later that year, she flipped a rental car into two parked cars. Her father blamed this accident on stress from the first accident.

Gayheart became well known from her appearances in a series of commercials for Noxzema skin cream beginning in 1991. In 1992, she joined the cast of the soap opera Loving. In 1993-1994 she had a recurring role in the Vanishing Son action pack series. In 1995, she had a recurring role in the series Beverly Hills, 90210. She has also been a regular on the television series Earth 2 (1994), Wasteland (1999), and Dead Like Me as Betty (2003) and has a re-occurring role on Nip/Tuck (2004).

She was initially hired to play the part of Inara Serra on Firefly (2002), but dropped out after only one day of filming. Morena Baccarin took over the role, and none of Rebecca's scenes were ever used.

She is currently playing Judy Nash in the new series Vanished.

Gayheart has appeared in several films, most often horror films or comedies aimed at a teenage audience: Somebody Is Waiting (1996), Nothing to Lose (1997), Scream 2 (1997), Hairshirt (1998), Urban Legend (1998), Jawbreaker (1999), Puppet (1999), From Dusk Till Dawn 3: The Hangman's Daughter (2000), Shadow Hours (2000), Doppelganger (2001), Harvard Man (2001), and Pipe Dream (2002).