Brees amassed 342 yards and hooked up with Robert Meachem three times for 119 yards and a score as the Saints (9-3) moved two games ahead of Atlanta in the NFC South.
The Falcons lost to Houston earlier Sunday.
The Saints benefited from 11 penalties for 109 yards racked up by the Lions, who were playing without suspended star defensive lineman Ndamukong Suh.
Matthew Stafford threw for 408 yards, with a touchdown and an interception, as Detroit (7-5) lost for the fifth time in seven games.
Swim Week Miami Beach 2014 [PHOTOS]