Updated

Michael Boley never stopped playing on - a 65-yard fumble return to the end zone.

Boley's score and a pair of Eli Manning touchdown passes boosted the Giants to a 28-16 win over St. Louis Monday night.

Sam Bradford drove the Rams into field-goal range, but when his behind-the- line-of-scrimmage pass to Cadillac Williams on the left side was dropped, Boley alertly picked up the loose ball and rumbled down the sideline to give the Giants a 14-6 lead with 10:58 left in the first half.

"It was a designed screen to Cadillac. I think they were bringing zero pressure, they were bringing someone off that edge, and I hurried and tried to get it around the guy and in doing that I threw it backwards," Bradford said. "I just can't do that. In hindsight I probably should have called a timeout and gotten out of that play."

The rest was easy for Boley, who was untouched to the end zone.

"Obviously, I read that it was a screen," Boley said. "I wasn't thinking it was a lateral at first but for us one of the things we talk about in practice is whenever the ball hits the turf is to pick it up and leave no doubt and always scoop and score. Right before I picked it up I didn't hear a whistle so I am just thinking score."

Manning completed 18-of-29 passes for 200 yards and was picked off once. Brandon Jacobs rushed for 50 yards and a score, but the win may have been costly for the Giants (1-1), as wide receivers Mario Manningham and Domenik Hixon both left with injuries. Manningham suffered a concussion, while Hixon sustained a right calf injury while making a juggling catch in the end zone for a 22-yard score with 21 seconds left in the second quarter.

"Tonight (we) lost a few guys, but hopefully they'll come back soon. But if not we'll just get some guys ready, make sure people know what they're doing," said Manning, whose team will play at Philadelphia Sunday. "We just got to go out there and execute better."

Bradford ended 22-of-46 for 331 yards with a TD. That went to Danario Alexander, who caught three balls for 122 yards.

Otherwise, the Rams struggled in the first matchup between Giants coach Tom Coughlin and his former defensive coordinator Steve Spagnuolo, now the head coach of St. Louis.

The Rams (0-2) played without running back Steven Jackson, who strained the quadriceps in his right leg during a season-opening loss to the Eagles.

Hixon's grab came just after Manning connected with Manningham for a 31-yard gain on the left side of the field. Manning's throw led Hixon past safety Craig Dahl into the end zone. Hixon juggled the ball with his right hand before finally coming down with it as he fell to the ground, but his knee seemed to buckle.

Josh Brown kicked a 27-yard field goal early in the third quarter to get the Rams within 21-9, but the Giants responded with a 10-play, 81-yard march, capped by a Jacobs nine-yard push into the end zone.

Bradford threw 19-yards to Alexander for a TD on the ensuing possession, which featured a fourth down connection to Mike Sims-Walker.

Neither team had a sustainable drive in the fourth quarter. In fact, the Rams never got past the 33, and that came in the waning minutes after Jacobs was stopped on a fourth down run. The Rams only went backwards with Bradford being sacked. Justin Tuck, who was out for the season opener with a neck injury, was credited with half-a sack on the play that led to the two-minute warning.

Quintin Mikell picked off Manning at the St. Louis 14 to end New York's first drive.

Alexander made a spectacular leaping catch along the left sideline, got up and turned it into a 68-yard gain before being tackled at the one. New York's defense stiffened and forced a Brown 21-yard field goal.

"We just couldn't finish it," Spagnuolo said of the red zone chances. "I don't have an explanation for you. I'd have to look at each one. There are some important things in this game. Third down is really important, red zone is really important and we didn't play well on third down and in the red zone."

The Giants caught a break later in the first quarter when Greg Salas muffed a punt return. Dave Tollefson recovered at the St. Louis 38. Manning's pass to Hakeem Nicks on 4th-and-4 fell incomplete, but cornerback Bradley Fletcher was flagged for pass interference, advancing the ball to the nine. Two plays later, Nicks caught a pass in the left side of the end zone for a three-yard score.

Brown split the uprights from 25 yards away for a 7-6 margin with 3:21 left in the opening quarter.

Game Notes

The Giants have won the last five meetings...Sims-Walker had six catches for 92 yards...New York's Ahmad Bradsahw had a game-high 59 yards on the ground and had five catches for 45 yards...The Rams had 59 yards rushing...The victory was the Giants' first at home on a Monday night since Oct. 18, 1999, when they defeated Dallas...The Giants won their fourth consecutive home opener.