Campbell is probably most famous for his portrayal of Rick Sammler on the ABC series Once and Again for which he received a Golden Globe nomination for Best Actor in a Dramatic Series. Among his other well-known roles are a gay gynecologist, Dr. Jon Philip Fielding, in all three of the television miniseries adaptations of Armistead Maupin's Tales of the City novels, and as Carter Buckley in seven episodes of the second season of television series The O.C.. He had a recurring role as Jordan Collier on the USA Network original series The 4400. His film credits include The Rocketeer, Bram Stoker's Dracula and Enough. He was also known for his recurring role as Detective Joey Indelli on the 1986-88 NBC series Crime Story.

Campbell's first prominent television role was that of Luke Fuller, Steven Carrington's lover on Dynasty during Season Five (1984-1985) and the beginning of Season Six (1985-1986.) Campbell was the second choice of the producers of Star Trek: The Next Generation (September 28, 1987 – May 23, 1994) to play the role of William Riker, but lost the role to Jonathan Frakes. Campbell would later appear as a guest star in the second season episode "The Outrageous Okona" (episode 2.4, first broadcast December 12, 1988.)

In 2000, he was named one of the "World's 50 Most Beautiful People" by People magazine.

Recently, he has made a successful career out of playing villains. One such role was as a college professor accused of raping a student (played by Shannyn Sossamon), on the episode "Doubt" of Law & Order: Special Victims Unit; it aired on November 23, 2004, as part of Season 6 (2004-2005.) In addition, he has portrayed serial killer Ted Bundy in the made-for-TV movie The Stranger Beside Me, and an accused serial killer who defends himself in the television series Shark.

Campbell was born in Charlottesville, Virginia. He has volunteered as an actor with the Young Storytellers Program. He is good friends with actor and Crime Story co-star Stephen Lang. Campbell recently portrayed General George Pickett in Gods and Generals, a part previously played by Lang in the film Gettysburg.

Campbell is a rugby enthusiast, having played rugby with the Chicago Lions RFC and the Santa Monica Rugby Club. He is cousin to Evil Dead actor, Bruce Campbell.