Mathews was born in Seattle, Washington and was two years old when he moved with his divorced mother to Janesville, Wisconsin. He attended Janesville High School, graduating in 1943. Mathews said that "a kind high school Teacher put me in a play, and that changed my life." According to a classmate, he was a "handsome rascal".
After moving to Los Angeles in 1954, Mathews acted at the Pasadena Playhouse, including a production of Comedy of Error. While there he met the head of casting for Columbia Pictures, leading to a seven-year studio contract.
Mathews' first sizeable role was as Lee J. Cobb's son in The Garment Jungle (1957). He was promoted to star for Tarawa Beachhead (1958), a war film produced by Charles Schneer. Schneer liked the actor's work and cast him in the role of Sinbad in The 7th Voyage of Sinbad (1958), directed by Nathan Juran with effects by Ray Harryhausen. The movie was a big success and remains Mathews' most famous film. Juran called Mathews "the epitome of professionalism."
Mathews co-starred with Van Johnson in The Last Blitzkrieg (1959), a war film for Sam Katzman, and Man on a String (1960) with Ernest Borgnine (Mathews replaced Cliff Robertson for the latter).. In The Last Blitzkrieg Mathews gave a strong performance in a role where he was cast against type, as a fanatical Nazi. He did an episode of Goodyear Theatre and went to Italy to make The Warrior Empress (1960) with Tina Louise. He was on stand by to replace Dirk Bogarde on Song Without End (1960) when Bogarde was clashing with the Director.
Schneer cast Mathews in an unofficial follow up to The 7th Voyage of Sinbad, The 3 Worlds of Gulliver (1960), playing the title role, with effects by Harryhausen. Columbia then put him in a prestigious film, The Devil at 4 O'Clock (1961), billed underneath Frank Sinatra and Spencer Tracy.
Mathews went to England to star in a swashbuckler film for Hammer Films released through Columbia, The Pirates of Blood River (1962). Edward Small cast him as Jack the Giant Killer (1962), directed by Juran, an attempt to repeat the success of Sinbad only without Harryhausen or Schneer.
Hammer called him back to play the title role in Maniac (1963), a psycho thriller released by Columbia. He then left Columbia.
He did another OSS 117 film, Panic in Bangkok (1964), then starred in The Viscount (1967), also from a novel by Bruce. In between he starred in a pilot for a TV show that did not go to series, Ghostbreakers.
Mathews starred in some low budget films, Battle Beneath the Earth (1968), and Un killer per sua maestà (968). He had a support part in A Boy... a Girl (1969) directed by John Derek and Dead of Night: A Darkness at Blaisedon (1969) a pilot for a proposed Dan Curtis series.
Mathews had support roles in Barquero (1970), the TV movie Death Takes a Holiday (1971), and Octaman (1971). He guest starred on General Hospital and Ironside. His last lead was The Boy Who Cried Werewolf (1973), directed by Juran.
He retired from acting in 1978 and moved to San Francisco, where he ran a clothing and antiques shop. Mathews died in his sleep in San Francisco on July 5, 2007, at the age of 81.
