Stafford threw two interceptions and lost a fumble and Bush fumbled once, but they overcame those problems to halt a two-game skid and move in front of the NFC North at 7-5.
The Packers (5-6-1) remained winless (0-4-1) since quarterback Aaron Rodgers suffered a broken collarbone Nov. 2.
The Lions came back from an early deficit to score 17 points in the second quarter, with Stafford throwing a 5-yard pass to Jeremy Ross and Bush running a yard for another score.
Stafford then threw a 20-yard touchdown pass to Calvin Johnson in the third period and found Kevin Ogletree with a 20-yarder in the fourth.
Detroit stifled Green Bay's offense, limiting the Packers to seven first downs and 126 total yards. The Lions piled up 562 yards.
The only Green Bay touchdown came one play after Stafford had fumbled he ball away at his own 1-yard line.
Stafford completed 22-of-35 passes for 330 yards while Bush picked up 117 yards on 20 carries.
The Lions hold a half game lead over Chicago for the division lead. Chicago will try to move back into a share of the top spot Sunday when it visits Minnesota.