Brees completed 30-of-42 passes for 313 yards and tossed two scoring strikes each to Marques Colston and Jimmy Graham as New Orleans (10-3) rebounded from last week's 34-7 loss to Seattle and solidified its grip on the NFC South.
Colston finished with nine catches for 125 yards, hauling in two second-quarter TD passes, and Graham snared six throws overall for 58 yards.
On defense, the Saints limited the Panthers to just 239 total yards.
Cam Newton made good on 22-of-34 passes for 160 yards with a TD and ran for 48 yards on six carries for Carolina (9-4), which fell one game behind the Saints in the division.
Should the two squads finish the season with identical records, New Orleans would win the division title in a tiebreaker.