Sale began the 2016 season winning each of his first 9 starts. He entered the All-Star Break with a 14–3 record (12 quality starts), an ERA of 3.38, and a WHIP of 1.04. Kansas City Royals manager Ned Yost named him the starter for the 2016 Major League Baseball All-Star Game. In the All Star Game, Sale pitched one inning and gave up a home run to Chicago Cub Kris Bryant.