Bithorn played for the San Juan Senators and at age 22 became the youngest manager in the history of Puerto Rican winter ball. Soon enough, he was pitching at Wrigley Field. On September 30, 1941, Bithorn was drafted by the Chicago Cubs and debuted in the Major Leagues on April 15 of the following year making history as the first Puerto Rican to play in the Major Leagues. Bithorn won nine games and lost fourteen in his first season, but he rebounded in 1943 by going 18-12 and completing 19 of his 30 starts, and leading the league in shutouts with seven, establishing a record for Puerto Rican pitchers that still stands.