The rushing yardage was a single-game franchise record.
Matt Moore, making his third straight start, threw three touchdown passes and completed 15-of-20 passes for 171 yards.
Steve Smith scored once on five catches for 60 yards.
John Kasay kicked two field goals, Brad Hoover and Mushin Muhammad scored touchdowns, while both Jon Beason and Richard Marshall made nine solo tackles for the Panthers (7-8), who have won three of four.
Eli Manning passed for 296 yards, one touchdown and two interceptions and also lost a fumble.
Mario Manningham caught six passes for 87 yards but lost a fumble.
Steve Smith caught a touchdown pass, and Lawrence Tynes kicked a 40-yard, third-quarter field for the Giants (8-7), who were out-gained 247-60 in rushing yards in their final game at the Meadowlands in East Rutherford, N.J.