EAST RUTHERFORD, New Jersey — Ten completions, four touchdowns.
"He went out there, made his throws and threw for four touchdowns," Bills coach Doug Marrone said of Orton.
"He knew exactly what he wanted to do. When you have a veteran quarterback like that, he's going to make the right plays."
Orton tied a career high with his four TD passes, and won for the third time in four games since replacing EJ Manuel as the starting quarterback for the Bills (5-3).
Orton finished 10 of 17 for 238 yards, connecting with Robert Woods, Lee Smith, Scott Chandler and Sammy Watkins for scores.
Watkins had three catches for 157 yards — but was embarrassed when he was caught from behind while celebrating early on what appeared would be a long TD. Without the injured Fred Jackson and C.J. Spiller in the backfield, the Bills rushed for just 67 yards.
But Stephon Gilmore, Preston Brown, Aaron Williams and Da'Norris Searcy had interceptions for the Bills, who sent the struggling Jets (1-7) to their seventh straight loss.
"No doubt, our defense is incredible and one of the best in the league," Orton said. "Any time your defense gets six turnovers, it makes your job easier."
The Jets have lost seven in a row for the first time since 2005, in Herm Edwards' final season as coach. Smith threw interceptions on three consecutive possessions in the first quarter and was pulled in favor of Vick, who was picked off once and lost two fumbles.
"Let me tell you," coach Rex Ryan said, "I'm getting sick and tired of the losing, that's for sure."
New York announced after the game that Smith had X-rays on his right shoulder after the game, but did not immediately announce results. The injury was not believed to have affected Smith's performance.
"We didn't execute," Smith said. "And when I say 'we,' I mean myself because it was just atrocious the way I started out."
Ryan didn't immediately announce whether Smith or Vick would start next week at Kansas City.
Percy Harvin, acquired last weekend by the Jets from Seattle, caught three passes for 22 yards and had 28 yards rushing on four carries in his debut with New York.
Buffalo got on the scoreboard on its first possession, with Orton zipping a pass to Woods for a 22-yard touchdown early in the first quarter.
Smith then threw three straight interceptions and was benched after the Bills turned the last interception by Williams into a score one play later, on Lee Smith's 1-yard touchdown catch with 4:36 left in the opening quarter.
Geno Smith finished 2 of 8 for 5 yards and the three interceptions as the Bills also became the first team to have that many in the first quarter since Arizona against Atlanta in 2012.
Vick jogged onto the field to loud cheers from the MetLife Stadium crowd, which had booed Smith moments earlier, and led the Jets on a 13-play, 76-yard scoring drive — capped by the first of Chris Ivory's two 2-yard touchdown runs.
But the Jets' defense gave up a huge play on the Bills' next possession as Watkins hauled in a long pass from Orton and took off down the field. But the rookie receiver looked up at the videoboard and pointed in premature celebration as New York wide receiver Saalim Hakim, put in on defense, caught him from behind. The play ended up as an 84-yard reception.
"I thought I was by myself and the guy ran me down and caught me," said Watkins, who later had a 61-yard TD catch. "I was shocked."
Two plays later, fullback Frank Summers pushed his way into the end zone from 2 yards to make it 21-7.
"It was a relief that we scored because I was upset," Watkins said. "I know I won't let it happen again."
Vick, 18 of 36 for 153 yards, was an early spark but wasn't without his share of mistakes. He had a 12-yard scramble negated by a questionable 15-yard taunting penalty when he spiked the ball on the sideline at the end of the run.
Two plays later, he took off for a 5-yard run but had the ball knocked out of his hands by Nigel Bradham.
"We were able to score 20 points off those turnovers and that's what means the most," Marrone said. "We had the potential to get more."
NOTES: Orton last threw four TD passes with Denver against Kansas City in 2010. ... Dan Carpenter hit the left upright on the extra point following Watkins' 61-yard TD. ... Vick finished with 69 yards on eight carries. ... Jets' Nick Folk kicked a 55-yard field goal, tied for second-longest in team history, as time expired in the opening half.