Thomas Tryon was born on January 14, 1926, in Hartford, Connecticut, as the son of Arthur Lane Tryon, a clothier and owner of Stackpole, Moore & Tryon. (He is often erroneously identified as the son of silent screen actor Glenn Tryon.)

He served in the United States Navy in the Pacific from 1943–1946 during and after World War II. Upon return from the U.S. Navy he attended and graduated from Yale.

Tryon then studied acting at NYC's Neighborhood Playhouse under the tutelage of Sanford Meisner. He appeared in the 1952 original Broadway production of Wish You Were Here, a long-running musical that starred Jack Cassidy, Patricia Marand and Sheila Bond.

Tryon married, in 1955, Ann L. Noyes, the daughter of stockbroker Joseph Leo Lilienthal and his wife, the former Edna Arnstein. She was the former wife of Thomas Ewing Noyes, with whom she had been a theatrical Producer. The Tryons divorced in 1958, and Ann Tryon resumed her previous married name, dying as Ann L. Noyes in 1966.

Tryon's film career began with Michael Curtiz directing him in a starring role in 1956's The Scarlet Hour, a crime drama about a man whose married lover persuades him to commit a robbery.

Future roles included comic horror and science fiction films, most notably I Married a Monster from Outer Space (1958) and the Walt Disney romantic comedy film, Moon Pilot (1962). He also appeared in Westerns, including Three Violent People (1956), with Charlton Heston and The Glory Guys (1965), as well as a made-for-TV remake of Winchester '73 in 1967.

Tryon also appeared in two epic films about World War II, The Longest Day (1962) and In Harm's Way (1965).

Tryon's greatest role was as an ambitious Catholic priest in The Cardinal (1963), for which he received a nomination for a Golden Globe Award for Best Actor – Motion Picture Drama. However, that honor barely compensated for the trauma and abuse he suffered at the hands of Director Otto Preminger. At one point during filming, Preminger fired Tryon in front of his parents when they visited the set, then rehired him after being satisfied that Tryon had been sufficiently humiliated.

Tryon's other television roles included that of Texas John Slaughter, a part of ABC's Walt Disney Presents in the late 1950s. The role was based on actual historical figure John Slaughter. Tryon also had guest appearances on NBC's The Restless Gun (as "Sheriff Billy"), The Virginian and ABC's The Big Valley (as "Scott Breckenridge") in the April 13, 1966 episode entitled ("The Midas Man"). He was part of a live television performance of The Fall of the House of Usher. He also co-wrote a song, "I Wish I Was," which appeared on an obscure record by Dick Kallman, star of the short-lived and now largely forgotten 1965 television sitcom, Hank. He appeared in the 1967 episode "Charade of Justice" of NBC's western series The Road West starring Barry Sullivan.

Disillusioned with acting, Tryon retired from the profession in 1969 and began writing horror and mystery novels. He was successful, overcoming skepticism about a classically handsome movie star suddenly turning Novelist. His best-known work is The Other (1971), about a boy whose evil twin brother may or may not be responsible for a series of deaths in a small rural community in the 1930s. He adapted his novel into a film released the following year, which starred Diana Muldaur, Uta Hagen, and John Ritter.

During the 1970s, he was in a romantic relationship with Clive Clerk, one of the original cast members of A Chorus Line and an interior designer who decorated Tryon's apartment on Central Park West in New York City, which was featured in Architectural Digest.

Harvest Home (1973), about the dark pagan rituals being practiced in a small New England town, was adapted as The Dark Secret of Harvest Home (1978), a television mini-series starring Bette Davis. An extensive critical analysis of Tryon's horror novels can be found in S. T. Joshi's book The Modern Weird Tale (2001).

Other novellas in the collection were based on the murder of former silent screen star Ramón Novarro, and the quasi-Oedipal relationship between actor Clifton Webb and his mother. Lady (1974) concerns the friendship between an eight-year-old boy and a charming widow in 1930s New England and the secret he discovers about her. Many consider this to be Tryon's best work. His novel The Night of the Moonbow (1989) tells the story of a boy driven to violent means by the constant harassment he receives at a summer boys camp. Night Magic, written in 1991, was posthumously published in 1995.

Tryon died of stomach cancer on September 4, 1991, at the age of 65, in Los Angeles, California.