Hoping to add to a three-game winning streak, the Broncos traveled to Charlotte, North Carolina for an interconference match-up with the Carolina Panthers at Bank of America Stadium. In the first quarter, the Panthers struck first, with quarterback Cam Newton connecting on a 4-yard touchdown pass to tight end Greg Olsen. However, the Broncos would reel off 29 unanswered points and dominate the remainder of the game. Quarterback Peyton Manning threw a 10-yard touchdown pass to wide receiver Brandon Stokley. The Broncos grabbed the lead in the second quarter, with return specialist Trindon Holliday returning a punt 76 yards for a touchdown, followed by a 53-yard field goal by placekicker Matt Prater, then in the third quarter, cornerback Tony Carter returned an interception off Newton 40 yards for a touchdown. Prater added a 27-yard field goal in the fourth quarter, followed by safety Mike Adams sacking Newton in the end zone for a safety. The Panthers responded in the fourth quarter, with a 5-yard touchdown pass from Newton to Olsen, but the Broncos put the game out of reach, with running back Ronnie Hillman rushing for a 5-yard touchdown. The Broncos' defense harassed Cam Newton throughout the game, sacking Newton seven times. This was Broncos' head coach John Fox's first visit to Carolina, where he served as head coach of the Panthers from 2002-2010.

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