Rising to 6'4", Selleck's dark hair, muscular and hairy-chested physique, sex appeal, trademark moustache, and good sense of humor make him popular for action, drama, and comedy parts; his Magnum role was a mix of all three.

After bit parts in film and TV as a contract actor for Universal Studios including Myra Breckinridge and a couple of failed pilots Selleck was awarded the role of Magnum that became a huge hit. Ironically Selleck, after years of little interest, was cast as Indiana Jones in Raiders of the Lost Ark that same year. Magnum's producers would not release the actor and he had to pass on the role, which then went to Harrison Ford.

Selleck starred in a number of film roles during and after Magnum; among the most notable were as an acrophobic police detective in Runaway and as a stand-in father in Three Men and a Baby. He also played the lead role in the Australian western Quigley Down Under. However, he never quite developed into a major film star, nor was he able to reestablish himself as the star of a regular TV series.

Selleck had a very successful recurring guest-star television role on the popular sitcom "Friends" as "Richard", an ophthalmologist friend of Monica Geller's father and, eventually, one of Monica's (ex-)boyfriends. Selleck also had a recurring role in the 1970s as Lance White in The Rockford Files. Lance was very trusting and always lucky, much to the surprise of Jim Rockford, the show's star private eye played by James Garner. Selleck's character was based on one played in Garner's earlier TV series Maverick (1957) by Selleck lookalike Wayde Preston in that series' highest-rated episode, "The Saga of Waco Williams."

Selleck has also appeared in a number of made-for-TV movies in recent years. In particular, he has sought to help bring back to popularity the western, often playing one of that genre's typical characters but thrust into a modern context.

Surprising many of his fans, Selleck unexpectedly played the role of General Dwight D. Eisenhower in the History Channel's 2004 made-for-TV movie Ike: Countdown to D-Day. The movie showed the planning, politics, and preparation for the 1944 Invasion of Normandy, and Selleck was critically lauded for playing a cool, calm Eisenhower.

Selleck is one of the few open conservatives in Hollywood. He is an outspoken member of the National Rifle Association, and in a well known incident he was verbally attacked by Rosie O'Donnell on her television show over his support of the NRA (before the show, she had promised not to bring up the subject, but says her temper got the best of her; also, this took place in the aftermath of the Columbine High School shootings in Littleton, Colorado). Selleck is a libertarian and is a registered Independent. He has appeared numerous times at fundraisers for the National Review, a conservative opinion magazine.

Selleck was married to actress Jacquelyn Ray from 1970 to 1982. He adopted Ray's son from a previous marriage, Kevin. He married actress Jillie Mack on August 7, 1987, and they have one daughter, Hannah. Selleck received an honorary doctorate from Pepperdine University. He was chosen because of his outstanding character and ethics. He is a board member of the non-profit Michael Josephson Institute of Ethics and co-founder of the Character Counts Coalition. He was chosen by People Magazine in 1998 as one of the 50 most beautiful people in the world.