Brees, who tossed five touchdowns in the win, finished the regular season with 5,476 yards. He passed former record-holder Dan Marino's mark in Monday's Saints victory over Atlanta.
NFC South champion New Orleans, however, missed out on the conference's No. 2 seed and a first-round playoff bye when San Francisco bested St. Louis elsewhere Sunday.
The Saints' Christopher Ivory rushed 19 times for 127 yards and a touchdown in the win.
Cam Newton was limited to 15-of-25 through the air for 158 yards, a touchdown and an interception, while running six times for 32 yards for the Panthers (6-10).