EAST RUTHERFORD, N.J. — New York Giants quarterback Eli Manning, who had been so pristine with his passing, threw five interceptions, two of which came in enemy territory, as the San Francisco 49ers edged New 16-10 at MetLife Stadium on Sunday.

It was the first multi-interception game since Week 2 for Manning, who finished 21 of 41 for 276 yards. It was also the first game in which he threw at least five interceptions since Dec. 15, 2013, in a 23-0 loss to Seattle.

The Giants, who hadn’t scored on their opening drive in 20 games, put an end to that streak this week thanks to a turnover by 49ers running back Frank Gore, who lost the handle on the ball on the Giants 16-yard line.

New York converted the fumble recovery into a 7-0 lead as Manning connected twice with receiver Rueben Randle for 38 yards, and running back Rashad Jennings, in his first game back from a knee injury suffered in Week 5, ran twice for six yards. Manning then capped the scoring drive by connecting with tight end Larry Donnell for a 19-yard touchdown and the 7-0 lead.

The maligned Giants defense, which last week allowed 350 rushing yards and which has been outscored 136-62 over the team’s four-game losing streak, actually kept this one close, holding the 49ers to just three first-half field goals of 31, 37, and 44 yards by kicker Phil Dawson, who gave his team a 9-7 lead at the half.

The 49ers scored their only touchdown of the game in the third quarter when quarterback Colin Kaepernick, who finished 15 of 29 for 193 yards, connected with receiver Michael Crabtree on a 48-yard touchdown pass to increase their lead 16-10.

The Giants, who upon winning the opening coin toss opted to defer, looked to create a spark in the second half when they ran a successful onside kick following Josh Brown’s 43-yard field goal, which closed the 49ers’ lead to 16-10.

However, the momentum gained from that onside kick was short-lived as, on third-and-9, Manning tossed his third interception on a ball intended for receiver Rueben Randle but which was picked off by 49ers safety Eric Reid and returned 51 yards.

The Giants did get one final opportunity to take the lead, this coming late in the fourth quarter. Manning connected with receiver Odell Beckham Jr., who finished with six receptions for 93 yards, on a spectacular 37-yard reception to give the Giants first-and-goal on the 49ers’ 4-yard line.

The Giants were unable to get into the end zone, as Manning threw three consecutive fade passes that went for naught before being picked off for the fifth time in the game on the fourth-down desperation play.

Next week, the Giants (3-7) will host Dallas Sunday night, while the 49ers (6-4) will host Washington.

Notes: With the loss, the Giants fell to 3-7 for the season. This is the first time since 1998, when Jim Fassel was the team’s head coach, that New York has posted a 3-7 record in their first 10 regular season games. That year, they went on to win five of their final six games to finish with an 8-8 record. … The 49ers improved to 21-9 in road games played under head coach Jim Harbaugh, who took over in 2011. With their won-loss road record improving to .700, the 49ers remain first in the NFL in road wins since the 2011 season. … The 49ers also improved to 3-0 against the NFC East this season, and have outscored three of the four NFC East teams played — Dallas, Philadelphia and the Giants — by a 60-48 margin. … Giants head coach Tom Coughlin fell to 5-2 against the 49ers and 15-14 overall against the NFC West. He was 3-4 against the NFC West as head coach to Jacksonville (1995-2002) and is now 12-10 against that division as head coach of the Giants.