Rex Reason attended Herbert Hoover High School in Glendale, California and enlisted in the United States Army at the age of seventeen, serving from 1946 to 1948.

Reason was under contract for two more years at Columbia until moving to Universal-International in mid-1953, after making a promising appearance in the sword-and-sandal epic Salome (1953) with Rita Hayworth.

The first of those was a syndicated western, Man Without a Gun (1957–1959), in the role of Adam MacLean, editor of the Yellowstone Sentinel newspaper in Dakota Territory.

In Perry Mason he played the role of defendant Steve Brock in the episode, "The Case of the Ancient Romeo" (1962) opposite Jeff Morrow, who had starred with him in This Island Earth.

Reason walked out on his film contract with Warner Bros. in the fall of 1961[5] when he was being considered for a starring role in John Frankenheimer's The Manchurian Candidate (1962).