In Week 4 of the 2016 season against the Atlanta Falcons, Anderson entered the game after an injury to Newton and threw for 172 yards, two touchdowns, and two interceptions as the Panthers lost by a score of 48–33. Due to Newton's injury, Anderson started the Week 5 game against the Buccaneers and threw for 278 yards and two interceptions as the Panthers lost by a score of 17–14. In Week 13 against the Seattle Seahawks, Anderson made his second start of the season. He threw an interception on the Panthers first play on offense and was then replaced by Newton. Anderson started the game due to Newton having violated the team's dress code. Anderson came into the 2017 NFC Wild Card Round on January 7, 2018 against the New Orleans Saints in the fourth quarter after Newton went down with an injury. He had one pass attempt in the 31-26 defeat.