The Packers made mistakes against the Lions, and Detroit took full advantage. Green Bay is now 2-2-1 after the 31-23 loss.
Aaron Rodgers lost two of the Packers' three fumbles, and Mason Crosby missed four field goals for the first time in his 12-year career.
Detroit's LaGarrette Blount ran for a pair of 1-yard touchdowns in the first quarter.
Davante Adams, Marquez Valdes-Scantling and Lance Kendricks all caught passes for touchdowns.
Rodgers completed 32 of 52 passes for 442 yards and 3 touchdowns.