It was the third victory in a row for the Steelers, who improved to 5-3 as they thoroughly outplayed New York in the second half to snap a four-game winning streak for the Giants, who fell to 6-3.
"That's as disappointing a loss as we've had around here in a long time," said Giants coach Tom Coughlin, who had wanted his team to provide some inspiration for the region in the wake of devastating superstorm Sandy.
Instead, Steelers quarterback Ben Roethlisberger got the better of fellow 2004 NFL Draft first-rounder Eli Manning in their third match-up after splitting their first two encounters.
Big Ben, who like Manning has two Super Bowl rings to his credit, outdueled his Giants' counterpart, making the big plays when needed and relying on a surprising fierce running attack.
An electrifying 51-yard catch and run connection from Roethlisberger to Mike Wallace cut the Giants' lead to 20-17 just 55 seconds into the final quarter.
After squandering a sure three points with a foiled fake field goal on a fourth-and-one from the New York three-yard line, the determined Steelers came back yet again with a nine-play, 51-yard drive for the game-winning touchdown.
Isaac Redman, the Steelers' third-string running back playing because of injuries, bullied his way over the goal line from one yard out to put the Steelers ahead with 4:53 left.
The touchdown capped a stellar game for Redman, who rushed for 147 yards on 26 carries for a Pittsburgh ground game that had ranked 21st in the league.
"A significant road win for us," Pittsburgh coach Mike Tomlin said. "He did a nice job of answering the bell and delivering for us."
The Giants and Manning, who made their own fourth-quarter comebacks seem nearly routine last season on their way to the NFL title, were held to three successive three-and-outs on their possessions in the fourth quarter to go out with a whimper.
"We've been pretty good in fourth quarters, coming back and scoring points and finishing games strong, and tonight we were in a position to score a touchdown and take the lead but we didn't come through," said Manning.
Roethlisberger completed 21-of-30 passes for 216 yards with two touchdowns and one interception.
Pittsburgh's defense, ranked number one against the pass, blanketed New York's receivers and limited Manning to just 10 completions in 24 passes for 125 yards and intercepted him once.
The Steelers outgained the Giants 349 yards to 182 and controlled the ball for over 35 minutes, more than 10 minutes longer than New York.
"Offensively, we didn't play well, didn't appear to be aggressive," Coughlin said. "We didn't tackle well, didn't stop the run well."
The Giants had the upper hand in the first half thanks to a strong pass rush.
Roethlisberger, who had been sacked just 13 times in seven games, was sacked three times in the first half with one of them leading directly to a New York touchdown.
Defensive end Osi Umenyiora came around behind Roethlisberger in the second quarter and hit his arm causing a fumble that was scooped up by linebacker Michael Boley who ran 70 yards for a touchdown and a 14-7 lead.
A late field goal pulled Pittsburgh within 14-10 at intermission. The Giants adding two field goals in the third quarter to pad their lead to 20-10 before the Steelers stormed back.