As a teen, he and his mother moved with his step-father, William Gilmore,[3] and half brother and sister to San Diego, California.

He recorded one of the earliest Vitaphone movie shorts called Carnival Night in Paris (Warner Brothers, 1927).

Ayres wrote, "I was a member of Henry Halstead's orchestra in 1927 at the Mission Beach Ballroom in San Diego, California for the summer.

His most successful movies at this time were those he made on loan to other studios, including The Doorway to Hell (1930) with James Cagney in a supporting role, and as Janet Gaynor's leading man in both State Fair (1933) and Servants' Entrance (1934), which featured a combination of live action and Walt Disney animation in a musical dream sequence, both for Fox Films.

[5] He moved to poverty row studio Republic Pictures to pursue a second career as a director, including the film Hearts in Bondage (1936), starring James Dunn and Mae Clarke.

Ayres played the role in nine films from 1938 to 1942 (and again in a 1950s radio series) while also appearing in light comedies for MGM, including Spring Madness and Rich Man, Poor Girl (both 1938), The Ice Follies of 1939 (1939), and Fingers at the Window (1942).

He returned to acting in the films The Dark Mirror (1946) with Olivia de Havilland and The Unfaithful (1947) with Ann Sheridan.

For his role in Johnny Belinda (1948) he received an Academy Award nomination for Best Actor; co-star Jane Wyman won for Best Actress.

He appeared (as the vice-president) in Advise & Consent (1962), and in The Carpetbaggers (1964), but he was, by then, primarily a television actor, with only occasional film work.

[6] Ayres guest-starred in an episode of The Bionic Woman ("Doomsday is Tomorrow", 1977) as Dr. Elijah Cooper, an elderly nuclear scientist who attempts to blackmail the world into peace.

He was one of 16 medics who arrived under fire during the invasion of Leyte to set up evacuation hospitals, and there he provided care to soldiers and civilians in the Philippines and New Guinea.

After the war, he resumed his career and made scores of movies, but never reached the peak of his early Hollywood stardom.