In 2016, Duvall was included on the Reds' opening day roster. By June, he led the NL in slugging percentage and was tied for first in MLB in home runs. He was selected to the 2016 Major League Baseball All-Star Game as a reserve. Duvall was the first University of Louisville alumnus to become an MLB All-Star. He also participated in the 2016 MLB Home Run Derby, losing to 2015 derby champion Todd Frazier in the semifinals. In his first full season in the majors, Duvall played in 150 games and posted a .241 batting average, 33 home runs, and 103 RBI.