Mizell's trade to the Pirates was one of the catalysts of Pittsburgh's championship run that season. Facing the Giants on June 16, 1960, he threw 166 pitches and stayed in the ballgame for three hours and two minutes, allowing two runs through eight innings before allowing three hits to start the ninth and getting charged with three more runs, though he still earned the win in the 10–7 victory. "Shucks, no. I wasn't tired," he quipped after the game. On the strength of two shutouts, he pitched 30 consecutive scoreless innings from July 22 to August 9, the longest such streak of his career. The first shutout may have been his best game of the season; he held the Cubs to two hits in a 4–0 victory on July 29. Six days later, he allowed five hits but no runs to the Giants, securing a 1–0 triumph. On September 18, he won another 1–0 game, limiting Cincinnati to three hits in nine innings. In the month of September, he had a 5–1 record and a 3.14 ERA as the Pirates clinched the NL pennant. Mizell went 13-5 for the Pirates that season (14–8 overall) and finished sixth in the NL in winning percentage (.636). Between St. Louis and Pittsburgh, he had a 3.50 ERA (3.12 with the Pirates), striking out 113 and walking 74 in 211 innings. Of the walks, 10 were intentional.