Leading the New York Giants 80 yards in just over a minute, Manning hit Jake Ballard for a 1-yard touchdown with 15 seconds left for a 24-20 win on Sunday, repeating a come-from-behind victory similar to the 2008 title game between the teams.
The Giants won that one, 17-14, on Manning's 13-yard scoring pass to Plaxico Burress with 35 seconds remaining. But on Sunday, it looked like the Patriots would win with a comeback of their own when Tom Brady threw a 14-yard pass to Rob Gronkowski, making it 20-17 with 1:36 to go.
But the Giants (6-2) had enough time. And they had Manning.
They were helped by a 20-yard pass interference penalty against safety Sergio Brown that put the ball at the 1 with 30 seconds left. Three plays later, Manning found Ballard in the back left corner of the end zone.
The loss put New England into a three-way tie for the AFC East lead with the Bills and Jets, who they visit next Sunday night.
After a scoreless first half, the Patriots took their first lead, 13-10, on Stephen Gostkowski's 45-yard field goal with 7:08 to go. Manning then led the Giants on an 85-yard march to a 10-yard touchdown pass to Mario Manningham with 3:03 remaining, putting the Giants on top 17-13.
The Giants won for the sixth time in seven games despite injuries that kept their top rusher, Ahmad Bradshaw, and leading receiver, Hakeem Nicks, from making the trip. But New York's defense pressured Brady much of the game, coming up with two sacks and two interceptions. New England also lost two fumbles.
Manning completed 20 of 39 passes for 250 yards with two touchdowns and one interception. Brady was 28-for-49 for 342 yards and two touchdowns.
Both quarterbacks struggled throughout the first half.
The offense was so bad that fans booed when Brady threw an incompletion toward Danny Woodhead with 8:30 left in the third quarter. They cheered on the very next play when Aaron Ross fumbled Zoltan Mesko's punt and Rob Ninkovich recovered at the New York 33.
But the Patriots managed just a 32-yard field goal by Gostkowski that cut the lead to 10-3.
The Giants punted on the next series and got the ball back when Spencer Paysinger recovered Julian Edelman's fumble.
Manning moved the Giants from the Patriots 40 to a third-and-goal at the 5, then threw an interception to Kyle Arrington in the end zone. Seven plays later, Brady hit Aaron Hernandez for a 5-yard touchdown, tying the game at 10 just 32 seconds into the fourth quarter.
The Giants had much better field position in the first half, starting at their 23, 22, 36, 28, 25 and 49. But all those series ended with punts.
The Patriots began at their 5, 6, 17, 20, 11 and 9. They punted four times and lost one interception before wasting their best scoring opportunity when Gostkowski pulled his 27-yard field goal attempt to the left with three seconds remaining. On that drive, the Patriots had five first downs, matching their total to that point.
Their next-best series of the half began at their 17 and ended on the first play of the second quarter. With the ball at the New York 29, Brady's pass was tipped by Michael Boley and intercepted by Mathias Kiwanuka, who returned it to the Giants 28.