New Orleans briefly tied the game on Jonas Sanker's scoop-and-score, but replay erased the touchdown and left Detroit ahead 7-0 in the second quarter.
Officials said Jared Goff had begun his throwing motion when Chase Young hit him, making the play an incomplete pass even though the ball traveled backward.
Fox rules analyst Mike Pereira said the quarterback's intent to throw forward controls the call once the motion starts, regardless of where the ball lands.
Detroit later punted on the drive and carried a 7-0 lead into halftime after a ruling that quickly became an early-season flashpoint over NFL pass-fumble interpretation.