Manning's third touchdown of the game, a 13-yard toss to Hakeem Nicks in the third quarter, gave the Giants their final margin of victory and boosted him past Phil Simms' former club record of 199 career TDs.
Manning completed 16-of-30 pass attempts for 249 yards and no interceptions. Nicks five grabs overall for 77 yards as the NFC East-leading Giants (7-4) broke a two-game losing streak.
Victor Cruz and Rueben Randle each made a scoring reception while New York's defense recorded five sacks.
Aaron Rodgers managed to complete only 14-of-25 passes for 219 yards, a touchdown and interception for the Packers (7-4), who fell one game behind the Chicago Bears atop the NFC Central.