In 1947, he was signed by the Cleveland Indians, eleven weeks after Jackie Robinson had been signed by the Brooklyn Dodgers. In his first year, he played 29 games, going at bat 32 times, and collecting 5 hits.
In 1948, he became an important piece of Cleveland's World Series victory; he also helped them to the American League pennant in 1954. In 1956, he was traded to the Chicago White Sox but he returned to Cleveland in 1958, for a short period of time. In 1959, he returned to the White Sox.
Doby finished his major league career in 1959, with the White Sox, after a short stint with the Detroit Tigers. He hit 253 career home runs, leading the American League twice (1952 and 1954). He hit 20+ home runs in a season eight consecutive years, and placed in the top ten of AL home run leaders seven years in a row.