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 serving in the Army Air Corps during World War II, he attended and performed at nearby Milton College for two years before transferring to Beloit College on drama and music scholarships. He remained at Beloit three years after graduation teaching speech and dramatic arts and appeared in regional theatre. He also taught high school English in Lake Geneva, Wisconsin. After moving to Los Angeles in 1954, Mathews acted at the Pasadena Playhouse, where he met the head of casting for Columbia Pictures, leading to a seven-year studio contract. He appeared in several action/adventure and fantasy films of the late 1950s and early 1960s. Mathews met his longtime partner Tom Nicoll, a British display manager at Harvey Nichols, a British luxury department store in 1961.

Although he felt typecast, he “looked fondly” on his Hollywood career, with his favorite role being Johann Strauss, Jr. in the Disney two-part telefilm The Waltz King (de) (1963). Matthews played Jean Bruce’s OSS 117 in two French films and played The Viscount based on another hero written by Bruce. He retired from acting in 1978 and moved to San Francisco, where he ran a clothing and antiques shop. He died in his sleep in San Francisco on July 5, 2007, at the age of 81. He was survived by his partner of 46 years, Tom Nicoll. The City of Janesville subsequently renamed a one-block street adjacent to the former Janesville High School “Kerwin Mathews Court”. The renovated building now houses the Janesville Performing Arts Center.