ORCHARD PARK, N.Y. >> After all these years, Tom Brady still has difficulty pinpointing a reason he and the Patriots consistently beat the Buffalo Bills.

Brady threw four touchdowns to up his career record to 23-2 against Buffalo in a 37-22 win Sunday. He went 27 of 37 for 361 yards to become the NFL’s fifth player with 60 300-yard games.

“I’m not sure really, historically,” Brady said. “I have a lot of respect for this team. They play hard every time we play them. I think we just come out on the winning end. It’s good to be on the winning end.”

Brandon LaFell scored on 17- and 56-yard passes less than six minutes apart in the fourth quarter. Tim Wright and Brian Tyms also caught touchdowns. The Patriots’ defense forced three turnovers and New England never trailed.

And it doesn’t seem to matter who’s signing the Bills’ checks.

Brady and the Patriots dominated their AFC East rival under the tenure of late Hall of Fame owner Ralph Wilson, who died in March. On Sunday, they spoiled the Bills’ new era under Terry and Kim Pegula, the Buffalo Sabres owners who completed their NFL-record $1.4 billion purchase of the team last week.

The Patriots (4-2) gained sole possession of first place in the division in moving ahead of the Bills (3-3). And they did so by beating Buffalo for the sixth straight time.

“It’s frustrating,” Bills tight end Scott Chandler said. “They’ve been the top dog in our division since the division was formed.”

LaFell, a newcomer in New England, isn’t surprise by the lopsided edge Brady has enjoyed over Buffalo.

“He’s a winner, man,” said LaFell, who had four catches for 97 yards. “That guy comes out every week and puts us in a situation to win games.”

And so much for questions about Brady being over the hill and the Patriots being vulnerable. Coming off a 43-17 win over Cincinnati, New England has won two straight since being blown out 41-14 at Kansas City on Sept. 29.

“I don’t pay attention to that noise,” receiver Julian Edelman said.

The Bills failed to build on the momentum of a thrilling come-from-behind 17-14 win at Detroit a week earlier. They let down a soldout crowd that was on its feet, chanting “TERR-RRY! TERR-RRY!” as Pegula and his entire family were introduced at midfield during a pregame ceremony

Once the game began, Buffalo’s offense was sloppy, and its defense uncharacteristically porous.

Kyle Orton went 24 of 38 for 299 yards with touchdown passes to Robert Woods and Chris Hogan. But he threw an interception and lost a fumble in his second start since taking over for EJ Manuel. Running back C.J. Spiller also lost a fumble, with the three second-quarter turnovers leading to 13 New England points.

“I’ve got to be better with the football,” Orton said.

The Patriots took control on their drives before and after halftime. New England went up 13-7 on Stephen Gostkowski’s 53-yard field goal to close the second quarter. Then the Patriots opened the third with the ball, and Brady efficiently capped a six-play, 80-yard drive with a 43-yard pass over the middle to Tyms, who outmuscled cornerback Stephon Gilmore and came down with the ball in the end zone.

Hogan’s 8-yard touchdown catch and Woods’ 2-point conversion pulled Buffalo within 30-22 with 5:58 remaining. But facing second-and-12 at his own 44, Brady hit LaFell up the right sideline for a touchdown to clinch the victory.

The Patriots overcame injuries to several starters. Linebacker Jerod Mayo did not return after hurting his knee in the first half. Running back Stevan Ridley did not come back after injuring his right knee in the third quarter. Guard Dan Connolly also sustained a concussion.

Patriots coach Bill Belichick said all three players would be evaluated, but specifically referred to Mayo’s injury as “a little bittersweet.”

NOTES: Brady is two 300-yard passing games shy of matching Brett Favre’s total. It was also Brady’s 16th career game with four or more touchdowns and no interceptions. … Chandler led Buffalo with six catches for a career-high 105 yards, becoming the team’s first tight end to surpass 100 yards since Pete Metzelaars had 113 on Sept. 13, 1992. … Patriots TE Rob Gronkowski had seven catches for 94 yards, but an 18-yard TD was nullified in the fourth quarter by a holding penalty against guard Jordan Devey.