ORCHARD PARK, N.Y. >> Rashad Jennings’ powerful 51-yard catch-and-run put an end to any fear of the New York Giants blowing another double-digit fourth quarter lead.

Jennings broke three tackles on his way up the left sideline midway through the fourth quarter to secure a 24-10 win over the Buffalo Bills on Sunday. If the outcome was ever in doubt, Giants cornerback Prince Amukamara settled it on Buffalo’s next possession by stripping the ball out of the hands of Bills receiver Robert Woods.

Eli Manning went 20 of 35 for 212 yards and three touchdowns — a 21-yarder to Dwight Harris and an 11-yarder to Rueben Randle — and an interception. The Giants defense then held the Bills in check in helping New York (2-2) win its second straight game.

The two wins came after New York opened the season by squandering 10-point fourth-quarter leads in consecutive games.

On Sunday, the Giants responded after the Bills cut the lead to 16-10 on Tyrod Taylor’s 23-yard touchdown pass to Karlos Williams with 9:41 remaining.

Facing third-and-3 at the New York 49, Manning dumped a short pass to his left to Jennings, who immediately sidestepped a tackle attempt by linebacker Nigel Bradham.

Jennings then raced up the sideline, where he avoided linebacker Preston Brown’s attempt to make a diving tackle from behind. And then Jennings shoved aside safety Bacarri Rambo before scoring.

The Bills (2-2) came completely unraveled.

Buffalo’s offense combined for just 77 yards and two first downs on its first nine possessions. Once it finally began moving, it came away with no points on two consecutive drives into the red zone.

Dan Carpenter missed a 30-yard attempt wide left with 2:20 left in the third quarter. Buffalo’s next drive ended when Dominique Rodgers-Cromartie and J.T. Thomas stopped Williams for no gain on fourth-and-goal from the 1.

Lack of discipline was a big issue for Buffalo. The Bills were flagged 17 times for 135 yards, two weeks after they were penalized 14 times for 140 yards in a 40-32 loss to New England.

Taylor had a 31-yard touchdown run in the third quarter negated by a holding penalty against Kraig Urbik. In the final minute of the game, Charles Clay’s 32-yard touchdown catch was nullified when Richie Incognito and Cordy Glenn were flagged for a chop block.

Manning’s interception — he was picked off by Stephon Gilmore at the goal line late in the fourth quarter — was his first of the season. He had attempted 142 passes without an interception.

The Giants went ahead for good late in the first quarter, when hit Dwayne Harris over the middle for a 21-yard touchdown. It came two plays after New York linebacker Devon Kennard intercepted Taylor’s pass up the left side intended for Clay.

Kennard was in stride with Clay and reached up at the last moment to snag the pass as the tight end was prepared to haul it in.

On the Giants’ next possession, Manning engineered a 10-play, 76-yard drive which he capped with an 11 yard pass over the middle to Randle. A Bills penalty — what else? — helped extend the Giants’ drive.

Rather than settle for a field goal on fourth-and-2 at Buffalo’s 25, the Giants picked up a first down when the Bills were penalized for an illegal formation.

The Bills were playing minus two stars with running back LeSean McCoy (hamstring) and receiver Sammy Watkins (calf) both sidelined by injuries.