Through the All-Star break in 2016, Quintana pitched to a 7–8 record with a 3.21 ERA in innings pitched. He was named to the MLB All-Star Game as an injury replacement for Danny Salazar. He finished the season 13–12 with a 3.20 ERA, striking out 181 batters while making 32 starts. Quintana finished tied for tenth in the voting for the American League Cy Young Award with Michael Fulmer, receiving one fifth place vote.