La Salle, one of four children, was born and raised in Hartford, Connecticut, by his mother, Ada Haynes. He is an alumnus of the Artists Collective, Inc. in Hartford. He attended the Juilliard School's Drama Division for two years as a member of Group 13 (1980–84), then attended New York University's Tisch School of the Arts, where he earned a Bachelor of Fine Arts degree in 1984.
At the time of his graduation from NYU, La Salle was cast in Joseph Papp's Shakespeare in the Park production of Henry V. Soon after, he found continuous acting work on Broadway, off-Broadway and in several daytime TV dramas including One Life to Live, where he played the reporter Mike Rivers.
In 1988, La Salle starred alongside Eddie Murphy in the movie Coming to America.
In 1994 the medical drama ER premiered on NBC with La Salle starring as Dr. Peter Benton. He held the role until leaving during the eighth season. In 2009, he returned to ER for two episodes (including the series finale) during its 15th and final season. He also returned to direct one episode.
He then played a Jamaican gangster in the independent film Johnny Was opposite Vinnie Jones, Samantha Mumba, Lennox Lewis, and Roger Daltrey. La Salle lived in Belfast, for four weeks while filming the movie, which he supported at the North American premiere of the film in 2006, at the American Black Film Festival in Miami.
He also starred in the Hallmark Channel original movie, Relative Stranger, which premiered on March 14, 2009. Also in the movie were Cicely Tyson as well as La Salle's former ER castmates Michael Michele (Dr. Cleo Finch) and Michael Beach (Al Boulet).
In 2010, La Salle played the United Nations Secretary General in the series finale of 24 and guest-starred in an episode of Covert Affairs in August of the same year.
In 2011, he played two recurring roles - one as a Caribbean community leader who rallied against the product Rasta Monsta in HBO's How to Make it In America, the second as the neuropsychiatrist E-Mo in CBS' A Gifted Man.
In 1996, La Salle made his directorial debut in the HBO made-for-TV movie Rebound: The Legend of Earl "The Goat" Manigault, starring Don Cheadle, James Earl Jones and Forest Whitaker, in which La Salle also played a pivotal role. Shortly after that, La Salle also directed the pilot for Soul Food: The Series on Showtime.
In 2002, he produced the feature film The Salton Sea with Val Kilmer and in the same year, he produced, directed and starred in the movie Crazy As Hell. In 2003 he wrote, directed and starred in an episode of The Twilight Zone and has subsequently directed multiple episodes of Law & Order: Special Victims Unit, CSI: NY, Ringer and A Gifted Man, as well as the 2012 Hallmark Channel movie, Playing Father.
After several years writing screenplays, LaSalle published his first novel in 2012, Laws of Depravity.