In 1951, Mizell pitched for the Houston Buffaloes of the Class AA Texas League. The team held a "Vinegar Bend Night," flying in 32 visitors reportedly from the town in Alabama for the evening's game. Because the town was so small, Mizell said that some of the guests "must've come from the suburbs." He had 15 strikeouts in that game, a 3–1 loss to the Shreveport Sports. In another outing, against the Dallas Eagles, he struck out 18 batters, tying the league's single-game record. Mizell led the league in strikeouts with 257, finished second in ERA to Tom Gorman (1.97 to 1.94), and tied for seventh in the league with 16 wins. With a record of 99–61, Houston won the pennant by 13.5 games over the San Antonio Missions.