Born and raised in Saint-Hyacinthe, Lamothe served in the Canadian Army during World War II, beginning his career in music by performing as "The Singing Sergeant" for his fellow soldiers. Following the end of the war, he recorded his first mini-album, Je suis un cowboy canadien, in 1946. He recorded a number of albums and singles over the next thirty years and frequently performed on tour, most frequently within Quebec but also from time to time in English Canada and at least one performance in Nashville. His performances included shows opening for Gene Autry at the Montreal Forum in 1952 and 1954.
Through the 1970s he performed as an actor in a number of films, most notably The True Nature of Bernadette (La Vraie nature de Bernadette) and The Death of a Lumberjack (Le Mort d'un bûcheron), and won the Canadian Film Award for Best Supporting Actor in 1973 for the latter role. During the same era, he was host of a television variety show, Le Ranch à Willie, for Télé-Métropole, and the subject of a documentary film, Je chante à cheval... avec Willie Lamothe, for the National Film Board.
He suffered a stroke while performing in Rimouski in 1978, and made only irregular appearances afterward, most notably in a CBC Television series about the history of Canadian country music in the 1990s. He was inducted as a Member of the Order of Canada in 1979.
His son Michel Lamothe, also sometimes credited as "Willie Lamothe, Jr.", is a former rock musician who was associated with the bands Offenbach and Corbeau.
Lamothe died on October 19, 1992 at age 72.