Manning completed 27-of-38 passes. His favorite target was Demaryius Thomas, who hauled down nine passes for 135 yards for the streaking Broncos (6-3).
Trindon Holliday returned a kick for a touchdown and Tony Carter added a score off an interception as Denver's defense delivered seven sacks in the victory.
The Panthers (2-7), meanwhile, fell for the sixth time in seven games despite a pair of TD passes from Cam Newton, who went 21-for-36 through the air with two pick-offs.
Greg Olsen made both scoring grabs, ending with nine receptions for 102 yards and the two scores in the loss.