Manning threw his 420th touchdown pass to move into a tie for second place on the NFL's all-time list with Dan Marino. He trails only Brett Favre (508).
Manning had plenty of help from his teammates.
Linebacker Von Miller harassed Cam Newton all day and Trindon Holliday returned a punt 76 yards for a touchdown as the Broncos (6-3) won for the fifth time in six weeks. The Broncos sacked Newton seven times, including once for a safety, and Miller pressured him into an interception Tony Carter returned 40 yards for a score.
Fox, who coached the Panthers for nine seasons, downplayed his return all week, but celebrated on the sideline with a few fist pumps Sunday.
After a strong start, Newton finished 21 of 36 for 241 yards with two touchdown passes to tight end Greg Olsen. He threw two interceptions.
But Newton spent most of this day on his back.
Miller, selected No. 2 in the NFL draft, one spot behind Newton last year, was a disruptive force right from the start, sacking Newton on the game's second series and then celebrated by imitating Newton's Superman routine, pretending to rip open his shirt.
Miller later forced a fumble.
The Panthers (2-7) appeared ready to give the Broncos a challenge early while playing in all-black uniforms, jumping to a 7-0 lead in the first quarter on a 4-yard pass from Newton to Olsen.
But it was all Broncos after that.
After a slow start, Manning started to pick apart Carolina's defense and was 16 of 20 for 135 yards and a 10-yard touchdown pass to Brandon Stokley in the first half as the Broncos methodically built a 17-7 lead.
With the game tied at 7, Holliday put the Broncos ahead with a nifty punt return for a controversial touchdown. As Holliday sprinted the final 25 yards to the end zone alone and untouched, television replays appeared to show him flip the ball out of his hand in celebration about a yard before he reached the end zone.
Although all NFL touchdowns are reviewed, there was no notification from the replay booth and the action continued with Matt Prater's extra point.
Prater later made it 17-7 on a 53-yard field goal.
Early in the third quarter, Charles Johnson sacked Manning and forced a fumble that Greg Hardy recovered. But on the next play Miller grabbed Newton's ankle in the backfield as he was trying to throw and Carter stepped in front of the pass near the sideline and returned it 44 yards for a touchdown and a 24-7 lead.
Prater added another field goal and Mike Adams sacked Newton for a safety to make it 29-7.