Darius Slay returned an interception 67 yards for a touchdown as the Lions cruised past the Cardinals 17-3 in the desert.
Zach Zenner had a one-yard touchdown run late in the fourth quarter to seal it for Detroit, which snapped a two-game skid to improve to 5-and-8.
The Lions managed just 218 yards of offense, while the Cards had 279.
Josh Rosen finished 26-of-41 for 240 yards and the pick-six for Arizona, which slipped to 3-and-10.
David Johnson was held to 49 yards on 15 carries in defeat.
The Lions play the Bills this Sunday at Buffalo.