Six months later, Manning grabbed his rightful place among the best in the game by delivering yet another crushing blow to Brady's Patriots, engineering his seventh fourth-quarter comeback of the season to lead the Giants to a 21-17 victory in Super Bowl XLVI at Lucas Oil Stadium on Sunday.
Having denied Brady and the Patriots a perfect season with a dramatic victory in Super Bowl XLII four years ago and executing another comeback victory at New England in Week 9 this season, Manning took advantage of a window left open by Brady to lead the Giants to their fourth in franchise history.
With the Patriots leading 17-15 and driving in Giants territory with under five minutes remaining, Brady was off the mark to a wide open Wes Welker, who was unable to reel in a twisting reception, and threw behind Deion Branch on consecutive passes. New England was forced to punt and give the ball back to Manning at the Giants' 12-yard line with 3:46 remaining to play, setting the stage for him to write another dramatic script.
On the first play of the drive, Manning went deep down the left sideline for a 38-yard completion to wide receiver Mario Manningham, who made a tremendous effort to keep both feet in bounds.
"He played a great game," Manning said of Manningham, who finished with 73 yards on five catches. "We knew they were going to double Hakeem Nicks and double Victor Cruz, and he was going to have to step up and make some big catches. None were bigger than that one down the sideline."
Eight plays later, the Patriots let running back Ahmad Bradshaw score from six yards out in an effort to save time on the clock.
Brady got the ball back at the 20-yard line with 1:04 remaining and completed a pass on fourth-and-16 to keep faint hope alive. But a Hail Mary pass as time expired fell incomplete.
For Manning, it was his seventh-fourth quarter comeback of the season. He won his second Super Bowl MVP in the process, giving him one more title than Peyton Manning in his brother's home stadium.
"It just feels good to win a Super Bowl," Eli Manning said. "It doesn't matter what stadium you're in."
Manning showed patience with the Patriots routinely playing both safeties deep, using a lot of underneath passes en route to completing 30-of-40 passes for 296 yards and a touchdown with a 103.8 passer rating. Nicks was his favorite target, catching 10-of-13 passes thrown his way for a game-high 109 yards.
"I'm just happy for the guys," Manning said. "I'm happy for everyone in this organization, Coach (Tom) Coughlin, all of my coaches, all of the players getting a chance to win the Super Bowl. Some of these guys are getting their first one. I feel great for them. I feel great for everyone."
Brady finished 27-of-41 for 276 yards, two touchdowns and an interception for a 91.1 passer rating. Tight end Aaron Hernandez led the Patriots with eight catches for 67 yards and a touchdown.
It appeared for much of the second half as though Brady, appearing in his record-tying fifth Super Bowl, would get his fourth ring and record-breaking 17th postseason victory.
After failing to get much started on offense through the majority of the first half and watching his defense play on its heels, Brady got the ball on his own 4-yard line with 4:03 remaining in the second quarter and began to carve out a few pieces of Super Bowl history.
Following a false-start, New England was backed up on its own 2-yard line when Brady went to work. He methodically moved the Patriots down the field, completing 10-of-10 passes for 98 yards. The final completion was a four-yard touchdown pass to running back Danny Woodhead, who had seven touches on the drive, and the Patriots had their first lead of the game at 10-9 going into halftime.
The 96-yard drive tied the longest in Super Bowl history, and the Patriots actually totaled 108 yards in total offense considering the false-start and a 10-yard holding penalty on right guard Brian Waters.
Brady wasn't fazed by the long intermission, coming out of halftime to cap an eight-play, 79-yard drive with a 12-yard touchdown pass to Hernandez.
That capped 17 unanswered points for the Patriots, with the touchdown to Hernandez marking the 16th straight completion — breaking Joe Montana's Super Bowl record of 13 consecutive completions.
The 3:55-minute drive still put the Patriots at a 9:30-second disadvantage in time of possession in the first half.
That's because the Giants dominated the early stages of the game, controlling the ball for 11:28 minutes of the first quarter. While New York was dictating the action, it still took a pair of Patriots miscues to build an early 9-0 lead.
After their opening drive stalled, the Giants opened the scoring on the Patriots' first offensive play. Standing in his own end zone, Brady was called for intentional grounding when he sailed an incomplete pass deep downfield while being pressured by defensive end Justin Tuck.
Up 2-0, the Giants got the ball back and marched the ball down the field, getting into New England territory with a 24-yard run by Bradshaw.
On their heels, the Patriots appeared to catch a huge break when wide receiver Victor Cruz was stripped of the ball by Sterling Moore following a third-down reception. But the Patriots were flagged for having 12 men on the field, and Manning connected on a 2-yard touchdown pass Cruz two plays later for the first touchdown of the game.
Manning finished the first quarter 9-of-9 passing for 77 yards, a touchdown and a 139.4 passer rating while completing passes to six different receivers. Manning set a Super Bowl record for the most consecutive completions to begin a game.
Game Notes: The Giants are the first team to win the Super Bowl after finishing the regular season 9-7. ... Giants tight end Travis Beckum suffered a torn ACL in the first quarter and did not return. Fellow tight end Jake Ballard suffered a knee sprain in the second half and did not return. ... Patriots tight end Rob Gronkowski was on the field for 21 of the Patriots' 29 first-half plays, although he was targeted just once by Brady and served primarily as a decoy while playing through a high left ankle sprain. Gronkowski was targeted just three times all game, including a deep heave from Brady that was intercepted by Giants middle linebacker Chase Blackburn.
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