Brees went 29-of-46 with a interception, compiling at least 300 passing yards for the eighth straight regular-season game -- one shy of his own NFL record. The Saints signal-caller also ran for a score.
Jimmy Graham made nine catches for 134 yards and two touchdowns.
Robert Meachem also corralled a scoring strike for New Orleans (3-0).
Arizona's Carson Palmer managed just 187 passing yards on 18-of-35 efficiency with two interceptions as the Cardinals (1-2) produced just 247 total yards of offense.