Hayes made his vaudeville debut with his mother at the age of six. In 1939, his mother sold some jewelry and borrowed $8,000 to open the Grace Hayes Lodge in Los Angeles, where he began working as a nightclub performer.

He appeared in films throughout the 1930s and 1940s, and had a significant television career in the 1950s. He often appeared with his wife Mary Healy. During World War II Hayes enlisted in the United States Army Air Forces and appeared in both the play and Winged Victory film of Winged Victory. In 1946, Hayes opened at the Copacabana in New York. This led to an engagement with the Dinah Shore radio show.

Hayes and Healy were the original singers of the Chevrolet jingle “See The U.S.A. In Your Chevrolet” in 1950. (Dinah Shore later sang the song for Chevrolet starting in 1952.) The couple starred in Zis Boom Bah (1941) along with Grace Hayes and were top-billed in the cult fantasy musical film The 5,000 Fingers of Dr. T. (1953). He also had a considerable reputation as a singer of comic songs, several of which made their way onto record, including “Life Gets Tee-Jus, Don’t It”.

In 1961, Hayes and Healy co-authored their biography, titled Twenty-Five Minutes from Broadway. The title was inspired by the name of the George M. Cohan musical Forty-five Minutes from Broadway, about the community of New Rochelle, New York where the two lived. They owned Columbia Island in New Rochelle, along the Long Island Sound shore. From that house, they broadcast a weekday breakfast conversation show on New York radio station 710 WOR.

Hayes may best be remembered for being designated substitute for Arthur Godfrey on both his CBS-TV and radio programs as well as several short-lived television series in which he and Healy co-hosted or co-starred, such as The Peter Lind Hayes Show (1950–51), Star of the Family (1950-1952), and Peter Loves Mary (1960–61). He also appeared on the pilot episode of The Match Game on December 5, 1962. He and his wife Mary were occasional guests on TV quiz shows To Tell the Truth, Password, and What’s My Line? In 1964, he appeared in an episode of The Outer Limits, titled “Behold, Eck!”, playing the lead role of Dr. Robert Stone, an absent-minded optical engineer and researcher.

Hayes was married to Mary Healy from 1940 until his death in 1998.