Born William Andrew Jones in the Wollaston neighborhood of Quincy, Massachusetts, De Wolfe was the son of a Welsh bookbinder who encouraged him to become a Baptist minister.

"[5] Billy De Wolfe also played the role of Pemberton Maxwell, The American Embassy's chargé d'affaires in the 1953 musical Call Me Madam.

Their screen chemistry in that film led to De Wolfe being quickly recast as a supporting character of Day in the 1951 production Lullaby of Broadway.

Wearing a hat and a shawl (but still sporting his mustache), De Wolfe (as old maid Phoebe Murgatroyd) would claim to be an expert on romance and answered questions from the lovelorn.

In 1972, De Wolfe was scheduled to return to Broadway in the role of Madame Lucy in the musical revival of Irene starring Debbie Reynolds, Monte Markham, Ruth Warrick, and Patsy Kelly.

Nevertheless, later that same year, De Wolfe recorded a vocal track for songs presented on the album Free to Be... You and Me, which was part of a children's entertainment project developed by actress and author Marlo Thomas.

His "closeted" homosexuality, however, is mentioned or alluded to in various publications, including in the 2004 volume Sir John Gielgud: A Life in Letters,[6] in a 2010 biography of actress Doris Day by author David Kaufman,[7] and in a 1998 article by Bruce Vilanch titled "America's favorite fruit" and featured in The Advocate.

[8] On February 26, 1974, suffering from an advanced case of lung cancer, De Wolfe was admitted to the University of California at Los Angeles Medical Center.