Bernsen was born in North Hollywood, California, the son of Harry Bernsen, Jr., a Hollywood producer, and veteran soap actress Jeanne Cooper, who appeared on The Young and the Restless. He graduated from Beverly Hills High School in 1972. Bernsen is also a "double Bruin," having received both a BA in Theatre Arts in 1977 and an MFA in Playwriting in 1979 from the University of California, Los Angeles (UCLA).
After a two-year appearance on the soap opera, Ryan's Hope, Bernsen was cast as lawyer Arnold Becker on the Steven Bochco television series, L.A. Law in 1986. The series became a hit, and the role earned him Emmy and Golden Globe nominations, appearances on magazine covers, and guest-starring roles on Seinfeld and The Larry Sanders Show. He remained on L.A. Law for the entire run of the show, until it ended in 1994.
Bernsen appeared with the British actor Bruce Payne in the films Kounterfeit and Aurora: Operation Intercept. He starred as the title character, Dr. Alan Feinstone, in the horror film The Dentist and its sequel. Bernsen was also cast as prima donna third baseman, Roger Dorn, in the sports comedy Major League and appeared in both of the film's sequels. Bernsen portrayed John Durant on General Hospital from September 2004 until the character was murdered in May 2006.
Bernsen played Jack Sherwood on Cuts, appeared twice on Celebrity Mole, and played a lawyer on Boston Legal. He appeared as Q2 on Star Trek: The Next Generation. He also had a recurring role as Captain Owen Sebring on the military drama JAG and played a Republican senator on two episodes of The West Wing. He directed, produced and appeared in the horror film Dead Air. Bernsen also co-starred in USA's Psych, playing the role of Henry Spencer, the father of the main character, Shawn Spencer (James Roday). In the film Rust, Bernsen played a former minister who returns to his hometown.
Bernsen appeared in 25 Hill, a film he produced, directed and wrote, which is centered around the All-American Soap Box Derby, and is planning a baseball movie about zombies, called "Three Strikes, You’re Dead."
He also appeared as a guest star in Switched at Birth, the ABC Family television series in season 1, episode 22 (2012), "Venus, Cupid, Folly and Time".
Bernsen was president and co-owner of Public Media Works, a new media company that develops entertainment for targeted fan bases. He directed and starred in Carpool Guy, the company's first film; it was targeted at soap opera fans and released on DVD in 2005.
Bernsen then went on to form Team Cherokee Productions with Kyle MacDonald, the blogger behind one red paperclip. According to the book One Red Paperclip, in June 2006, Bernsen traded a role in the film Donna on Demand to MacDonald for a snow globe of the band KISS. It was for this role that MacDonald eventually traded for a two-story farm house.
In recent years, Bernsen has focused on making Christian-themed films. His first such film was Rust, released in 2010 by Sony Pictures. Bernsen, along with producing partner Chris Aronoff, formed Home Theater Films, an independent production company that, develops, produces, and markets films and television shows for the Christian market. 25 Hill, the company's first title, was released in July 2012. This was followed by 3 Day Test (2012), Beyond the Heavens (2013), and Christian Mingle (2014).
In October 2015 Bernsen's debut novel was released by Pelican Book Group. The book, Rust: the Novel, is an adaptation of Bernsen's 2010 feature film, Rust, in which he played the main character as well as served as writer and director.
Bernsen has been married to British actress Amanda Pays since 1988. They have four sons: Oliver, Angus, Henry and Finley. Bernsen was married to Brenda Cooper from 1983 to 1987.
In 2008, Bernsen and his family appeared on the ABC show Celebrity Family Feud, defeating the Margaret Cho family before losing to the crew from American Chopper.
Bernsen has one of the largest snow globe collections in the world, with 8,000 globes.