As a child, Gibson enrolled in Little Theater School and later graduated from Bishop England High School. He then attended the College of Charleston (1979–1981) and became an intern at the Alabama Shakespeare Festival, where he was encouraged to apply to the prestigious Juilliard School. After a year and a half at Charleston, Gibson won a scholarship to Juilliard’s Drama Division (Group 14: 1981–1985), where he graduated with a Bachelor of Fine Arts degree in 1985.

Gibson’s first television appearance was in 1987 in a guest role on the legal drama Leg Work, followed by stints on the daytime dramas As the World Turns and Another World. In 1992, Gibson made his movie debut in Ron Howard’s Far and Away, in which he portrayed Stephen Chase. Chase was the villainous rival of Joseph Donnelly (Tom Cruise) for Shannon Christie’s (Nicole Kidman) affections. His next lead role was in 1993 as David, a gay waiter, in Denys Arcand’s Love and Human Remains. Also in 1993, he played bisexual businessman misanthrope Beauchamp Day in the television version of Armistead Maupin’s Tales of the City(1993). At the time, Tales of the City was highly controversial for its gay, transgender, bisexual and drag queen characters along with nudity, sexual situations, drug use and explicit language. Gibson later reunited with Arcand in Stardom (2000). Gibson then returned to television when portraying Dr. Danny Nyland on the medical drama Chicago Hope from 1994 to 1998. From 1997 to 2002, Gibson portrayed Greg Montgomery in the sitcom Dharma & Greg, for which he was nominated twice for a Golden Globe Award. After Dharma & Greg, Gibson appeared in various TV movies.

Gibson previously directed six episodes of Criminal Minds since 2013, along with two last season episodes of Dharma & Greg in 2001. Gibson had a prior altercation with an assistant director and had undergone anger-management counseling at that time.

In 2005, he was cast as Supervisory Special Agent Aaron “Hotch” Hotchner, the unit chief of the Behavioral Analysis Unit (BAU) team, in the series Criminal Minds.

Gibson resides in San Antonio, Texas. His son, Travis Carter, was featured in the season 10 episode “Boxed In” (#5) of Criminal Minds as a friend of the kidnapped child. Gibson and his wife Christine separated in 2011 and in 2014 he filed for divorce. The divorce was finalized on February 14, 2018.

On August 11, 2016, Gibson was suspended (after appearing in two episodes of the twelfth season of Criminal Minds) following an on-set altercation with a writer-producer; he apologized for the confrontation in a statement, claiming the dispute arose from creative differences in an episode he was directing.