On May 7, 2016, Canó hit his 250th career home run, joining Joe Gordon and Jeff Kent as the only second basemen to reach 250 career home runs within the first 12 years of their career. He was selected to his seventh All-Star Game, played at Petco Park in San Diego. On August 28, Canó reached 30 home runs for the second time in his career, hitting it against the Chicago White Sox. In 161 games, Canó finished the season with a .298 batting average, 195 hits, 33 doubles, 39 home runs, and 103 RBI.