On February 10, LaVine scored a season-high 46 points with nine 3-pointers in a 129-116 victory over the New Orleans Pelicans. With a new head coach in Billy Donovan and averaging career highs in scoring and shooting efficiency, on February 24, 2021, he was named a reserve for the 2021 NBA All-Star Game. It was his first All-Star selection and the first Bulls player selected since Jimmy Butler in 2017. In the 34th game of the season, LaVine had his 17th game scoring 30 points or more. On March 7 he played 28.19 minutes and scored 13 points during the All-Star game. For the season, he averaged a career-high 27.4 points per game, which ranked seventh in the NBA. He also reached career highs in rebounds (5.0), assists (4.9), 3-point shooting (41.9%), overall field goal percentage (50.7), and free throw percentage (84.9).