Coming off their bye, the Giants (7-4) put to rest concerns about a dormant offense and a tired arm for Manning. He connected with rookie Rueben Randle, Victor Cruz and Hakeem Nicks for scores, and Ahmad Bradshaw had a combined 119 yards, including a 59-yard sprint on a screen pass to begin the onslaught.
The Giants opened a two-game lead in the NFC East.
Mathias Kiwanuka had two of the sacks as Rodgers never got comfortable. Green Bay (7-4) had its five-game winning streak snapped and fell out of a tie atop the NFC North with Chicago. The Packers had allowed no more than 24 points during their string of victories.