Brees was 26-for-34 for 358 yards.
The veteran quarterback connected with Jeremy Schockey on 1- and 15-yard passes and added TD strikes of 9 yards to Marques Colston, 39 yards to Robert Meachem, 58 yards to Devery Henderson and 13 yards to Heath Evans.
Mike Bell carried 28 times for 143 yards for the Saints (1-0).
Detroit quarterback Drew Stafford was16-for-37 (205 yards) and ran for a touchdown, but he was intercepted three times.
Louis Delmas returned a fumble 65 yards for one Detroit score.
The Lions (0-1) have lost 18 straight games over three seasons.