On January 14, 2021, after getting 16 points, six rebounds, and a season-high 12 assists in a 111–108 win against the Charlotte Hornets, Lowry recorded his 4,000th assist with the Raptors, joining Stephen Curry and Damian Lillard as the only players who have over 4,000 assists with their current teams. On January 27, 2021, after a quick three-pointer against the Milwaukee Bucks, Lowry reached 10,000 points with the Raptors, joining Chris Bosh and DeMar DeRozan as the only players to reach that milestone with the franchise. He had 21 points, five rebounds and three assists in a 115–108 loss. On January 31, 2021, Lowry had 12 points, six rebounds, and a season-high 15 assists in a 115–102 win against the Orlando Magic. On February 2, 2021, Lowry had his first triple-double of the season, getting 14 points, 10 rebounds, and 10 assists in a 123–108 win against the Magic. On February 5, 2021, Lowry scored a season-high 30 points with five rebounds, seven assists and two steals in a 123–117 win against the Brooklyn Nets. On February 26, 2021, Lowry had his second triple-double of the season with 20 points, 11 rebounds and 10 assists in a 122–111 win against the Houston Rockets. On March 4, 2021, Lowry had a career-high 19 assists in a 132–125 loss against the Boston Celtics.