During eleven seasons in the major leagues, Johnston played for the Cincinnati Reds, Cleveland Indians, Pittsburgh Pirates, and Philadelphia Athletics. He batted .263 (992-for-3774) with 14 home runs, 478 runs and 381 RBIs, and was a member of the Indians team that won the 1920 World Series. His brother Jimmy Johnston was also a major league player.
Doc played against his brother Jimmy in the 1920 World Series, with Doc playing for Cleveland and Jimmy on the Brooklyn Robins. It marked the first World Series and first Big Four championship to feature two brothers on opposing teams.

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