Brady threw a 69-yard touchdown pass to Julian Edelman midway through the fourth quarter, and New England beat the San Diego Chargers 23-14 for its eighth win in nine games.
The Patriots (10-3) clinched their 12th straight 10-win season for the second-longest such streak in NFL history. They spent the week in San Diego following a loss at Green Bay in order to cut down on late-season travel.
The Chargers (8-5) looked almost like a road team, getting shut out in the second half as a large portion of the crowd cheered for the Patriots.
"We worked very hard this week," Patriots defensive tackle Vince Wilfork said. "Being in San Diego for a week gave us a chance to bond a little bit, watch extra film because we was at the hotel, and basically hung out and talked football. ... A lot of times we talked about what it's going to take to win a football game. Everybody prepared well. ... The focus was unbelievable."
New England went ahead 16-14 on Stephen Gostkowski's 38-yard field goal with 10:34 left.
After forcing the Chargers to punt, the Patriots started on their 31. Brady faked a handoff and hit Edelman on a slant at about the 45. He broke two tackles and was gone.
"Tommy put a good ball out there," Edelman said. "And I did my job to get open and try to catch the ball and do something with it."
Said Brady: "We needed that play. We were struggling. We needed a great play."
Brady completed 28 of 44 passes for 317 yards and two touchdowns with one interception. Edelman caught eight passes for 141 yards.
San Diego's offence scored one touchdown.
"We just didn't play well," quarterback Philip Rivers said. "They were the reason for a lot of that. But we had some things that were self-inflicted as well. It wasn't our best day, obviously. Anytime you score seven points in this league you're not going to win any games."
Brady said the Patriots' defence "was unbelievable. They kept us in it all night. That was a defensive win right there. I love the way those guys played on defence."
The game had several momentum swings.
After Gostkowski kicked his second 22-yard field goal of the first half, Brandon Bolden blocked a punt by Mike Scifres to give New England the ball on the San Diego 28. Scifres hurt his left shoulder on the play and was carted off the field.
Four plays into the drive, Rob Gronkowski caught a 14-yard touchdown pass to pull the Patriots to 14-13.
Gronkowski became the first tight end in NFL history with four seasons of 10 or more scoring receptions.
The Chargers scored twice in 2 minutes, 33 seconds in the second quarter.
Safety Darrell Stuckey returned a fumble 53 yards for a touchdown and Malcom Floyd made a diving catch of a 15-yard touchdown pass from Philip Rivers.
Manti Te'o leaped to make his first career interception just before halftime, preserving the Chargers' 14-13 lead.
With the Patriots looking to go ahead, Brady tried to hit Gronkowski on second-and-10 from the Chargers 18. But Te'o, the second-year linebacker from Notre Dame, picked off the under-thrown pass at the 4.
Rivers completed 20 of 33 passes for only 189 yards.
New England's Brandon Browner was whistled for a personal foul for hitting Chargers tight end Ladarius Green in the head with his shoulder in the third quarter. The penalty nullified an interception return for a touchdown by Devin McCourty.
"When you can make a play like that even though it's erased, that's a big hit," McCourty said. "It's tough for refs to make that call. It happened so fast, two guys moving. We're all telling B, 'Good hit.'"
After lying on the ground for several minutes, Green walked off the field although he appeared wobbly.
NOTES: Brady improved to 6-0 against Rivers. ... Patriots owner Robert Kraft took a helicopter to the game after watching his New England Revolution lose the MLS Cup to the LA Galaxy in Carson.
Online: http://pro32.ap.org/poll and http://twitter.com/AP_NFL