Born in Fulton, New York, he was a right-handed pitcher who appeared in 385 games in Major League Baseball over ten seasons (1944–53) as a member of the St. Louis Cardinals, Pittsburgh Pirates and Cleveland Indians.

In his major-league career, Wilks compiled a 59–30 record in his 385 appearances, 341 of them as a relief pitcher, with a 3.26 earned run average and 46 saves, 22 complete games and five shutouts.

As a Cardinal, he was a member of two World Series championship teams, defeating the St. Louis Browns in 1944 and the Boston Red Sox in 1946.

In World Series play, he compiled an 0–1 record in three appearances, with a 4.91 earned run average and seven strikeouts.

While pitching with the Cardinals in 1947, he attempted to organize a boycott so as not to have to play a desegregated Brooklyn Dodgers with Jackie Robinson.