McCaffrey rushed for a 9-yard run to break the record established by DeAngelo Williams, who accumulated 1,636 yards in 2008. Williams had 1,515 rushing yards and 121 receiving yards that season.
The 22-year-old McCaffrey finished Monday's game with 120 yards from scrimmage (53 rushing, 67 receiving) to boost his season total to 1,747 (979 rushing, 768 receiving). He has already set franchise records for receptions (94), receiving yards and receiving touchdowns (six) by a running back.
McCaffrey also showed off his arm with a 50-yard touchdown pass to tight end Chris Manhertz in the first quarter.
For his efforts, McCaffrey became the first player with 50 yards rushing, receiving and passing in a game since Pro Football Hall of Famer Walter Payton accomplished the feat on Dec. 22, 1985.
McCaffrey's heroics aside, the Panthers (6-8) have lost six straight contests and are all but eliminated from playoff contention.
The slumping Panthers host the Atlanta Falcons (5-9) on Sunday (1 p.m. ET).