Medwick entered professional baseball with the Scottdale Scotties of the Middle Atlantic League in 1930. In 75 games with the Scotties, he had a .419 batting average and 22 home runs. He spent most of the next two seasons with the Houston Buffaloes of the Texas League. He played 161 games for Houston in 1931, hitting .305 with 19 home runs. He played in 139 games for the team the next year, hitting .354 with 26 home runs before being called up to the major leagues.