Manning, who threw for a career-best 510 yards and three touchdowns against Tampa Bay on Sunday, completed 27 passes for 288 yards and a touchdown before being relieved by backup David Carr in the fourth quarter as the Giants improved to 2-1.
Manning, last season's Super Bowl Most Valuable Player, outshone NFL rookie of the year Cam Newton, who had a tough time against the Giants defence, completing 16 of 30 passes for 242 yards with three interceptions as the Panthers fell to 1-2.
While New York kept the dynamic Newton in check, holding the slippery quarterback to just six yards rushing on six carries and one touchdown, Manning shredded the Carolina defence and manufactured points from the Giants' first four possessions.
New York took the opening kick-off and marched 80 yards in eight plays, Manning firing a 14-yard touchdown strike to Martellus Bennett as the Panthers allowed their opponent to score on the opening drive for the third consecutive game.
"We talked about getting a fast start, jump out to a lead," Manning said. "Get the ball, go 80 yards for a touchdown, that was a great start.
"It set the tempo for the whole game and we kept it going."
Lawrence Tynes booted a 47-yard field goal to give the visitors a 10-0 first quarter advantage and the Giants kept up the pace in the second, scoring on their first possession when Brown barrelled over from a yard out and Tynes kicked a 49 yarder to make it 20-0 at halftime.
Brown, getting his first start in place of injured Ahmad Bradshaw, ran for a career high 113 yards on 20 carries.
The second half was more of the same, the Giants capitalising on a Panthers turnover to go 23-0 ahead with a 30-yard Tynes field goal.
The Panthers offence finally let loose and Newton led a 13-play drive before diving over for a touchdown from the one yard line.
Tynes was on target again with a 36-yard field goal to pad New York's lead to 26-7 entering the final quarter.
In the fourth, Brown ran in another one-yard touchdown and Tynes completed the rout with a 27-yard kick, his fifth field goal of the game.
"We played well but settled for too many field goals maybe," said Manning. "But we had a good game plan and ran the ball really well.
"When we can run the ball everything starts clicking."
- Cam Newton