Desmond was selected as an American League All-Star to represent the Rangers at the 2016 Major League Baseball All-Star Game in San Diego along with teammate Cole Hamels. Prior to the game, Desmond was batting .322 with 15 home runs and 55 RBIs. Desmond finished the 2016 season with a batting average of .285, 22 home runs, and 86 RBIs. The Rangers lost in the 2016 ALDS, being swept by the Blue Jays in three games. In the series, Desmond went 3-for-14 (.214) with two runs batted in (RBI), collecting all of his hits and RBIs in the same game (Game 2) for his third and final three-hit game in the postseason.