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Jeff Wilson Jr. rushed for a career-high three touchdowns and 112 yards before leaving with an ankle injury and the San Francisco 49ers dominated in a 33-6 win over the New England Patriots on Sunday.

49ers quarterback Jimmy Garoppolo finished 20 of 25 for 277 yards with two interceptions in his first game against his former team. San Francisco (4-3) has followed back-to-back losses with two wins and is 3-0 on the road.

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The Patriots' 27-point loss was their largest at home under Bill Belichick, according to Elias Sports Bureau. They had gone 286 games without a three-game losing streak, the longest span between three-game slides in NFL history. New England fell to 2-4 for the first since coach Belichick’s first season in 2000, when the Patriots went 5-11.

New England was outgained 467-241 in total yards.

San Francisco's Brandon Aiyuk had six catches for 115 yards and Deebo Samuel had five catches for 65 yards before leaving the game with a hamstring injury.

Patriots quarterback Cam Newton struggled throughout, completing 9 of 15 passes for 98 yards and three interceptions before being replaced by Jarrett Stidham in the fourth quarter. Stidham was 6 of 10 for 64 yards and an interception.

Newton was out of sync from the outset, making poor reads and poorer throws. But Garoppolo was successful in spreading out New England’s defense with a steady diet of passes behind the line scrimmage and jet sweeps to get the ball in the hands of Wilson, Samuel and George Kittle.

San Francisco dominated the first half, taking a 23-3 lead, holding the ball for 22:30, and racking up a 301-59 advantage in total yards. The Patriots also managed just four first downs to the 49ers’ 18.

The Niners took just over five minutes and nine plays to march 75 yards and take a 7-0 lead on 3-yard run by Wilson. It was the first time the Patriots have allowed a touchdown on an opponents’ opening drive at home since Week 4 of 2016 against Buffalo.

Following a Patriots punt, San Francisco was pinned inside its 15. Long completions by Garoppolo helped erase some early penalty losses before he missed high on a pass for Kittle and was intercepted by Devin McCourty.

San Francisco’s defense limited the damage, yielding a 40-yard field goal by Nick Folk.

That wasn’t the case for the Patriots’ defense later in the second quarter.

Trailing 10-3, Newton made a bad developing play worse when he tried to dump off the ball on the run to receiver Jakobi Meyers. It was picked off by linebacker Fred Warner. Five plays later the 49ers capitalized on a 4-yard touchdown run by Kyle Juszczyk.

The lead grew to 23-3 with just under a minute to go before halftime on a 16-yard run by Wilson.

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INJURIES

49ers: Wilson Had just crossed into the end zone following his third TD when his leg twisted as he was tackled. He stayed down on the field before being able to walk off under his own power.

Patriots: WR N’Keal Harry left with a head injury and did not return. … LG Joe Thuney departed with an ankle injury. … RT Justin Herron also left with an ankle injury.

UP NEXT

The 49ers head to Seattle next Sunday. The Patriots visit Buffalo.