Derringer won 40 games at Rochester in the International League and led them to two pennants in 1929 and 1930. He helped the Cardinals win the pennant with an 18-8 mark in 1931, but was traded to the Reds in 1933. He started and won the first major league night game at Cincinnati in 1935. Hurling three consecutive 20-win seasons (1938-40) and going 25-7 in 1939, Derringer led the Reds to two successive pennants and the World Championship in 1940. He was the winning pitcher in the 1940 All-Star Game and had two one-hit games that same season.
Derringer led the league in winning percentage in 1931 and 1939, games lost in 1933, games started in 1936, 1938, and 1940, and complete games and innings pitched in 1938. He had 32 career shutouts, won ten 1-0 complete games, and had a 1.88 walk ratio. He was sold to the Cubs in 1943 and helped them capture the pennant in 1945.