In the Pacers' 2015–16 season opener against the Toronto Raptors on October 28, George recorded 17 points on 4-of-17 shooting and 12 rebounds in a 106–99 loss. After publicly criticizing the referees following the game, he was fined $10,000. On November 6, he scored 36 points in a 90–87 win over the Miami Heat. Three days later, he scored 27 points, including a career-high 19 points in the first quarter, to lead the Pacers to a 97–84 win over the Orlando Magic. On November 24, George scored 40 points and made seven three-pointers, part of a franchise-record 19 by the Pacers in a 123–106 victory over the Washington Wizards. On December 3, he was named the Eastern Conference Player of the Month for games played in October and November. George led the Eastern Conference and ranked fourth in the NBA in scoring (27.2 ppg), helping the Pacers win 11 of 13 games after an 0–3 start. Two days later, he scored a career-high 48 points in a 122–119 overtime loss to the Utah Jazz. George competed for the Eastern Conference in the 2016 NBA All-Star Game in Toronto, where he started and was the game's leading scorer with 41 points, finishing one point shy of the All-Star game record set by Wilt Chamberlain (42) in 1962. On March 19, he had a 45-point game in a 115–111 loss to the Oklahoma City Thunder. George helped the Pacers return to the playoffs in 2016, finishing as the seventh seed in the Eastern Conference with a 45–37 record.