After a disappointing loss to Seattle the Patriots traveled to Santa Clara, CA to face Tom Brady's childhood team, the San Francisco 49ers, who were on an eight-game losing streak. This was also the first time Brady played the 49ers in San Francisco, as he missed the Patriots' trip to Candlestick Park in 2008 as a result of an injury. After a 49ers three-and-out, Amendola returned the punt 30 yards to the 49ers 27. Six plays later, Brady hit Edelman on a 7-yard touchdown pass, but Gostkowski missed the extra point. The 49ers drove all the way to the Patriots 6 on their next drive, but Hightower sacked Colin Kaepernick for a 9-yard loss on 3rd-down and they were forced to settle for a 33-yard field goal by Phil Dawson. The Patriots countered on their next drive, racing 77 yards in just 6 plays, scoring on Brady's 9-yard touchdown pass to James White, increasing the lead to 13-3. Two possessions later, the 49ers raced 92 yards in just over four minutes, scoring on an 18-yard touchdown catch by Vance McDonald, trimming the deficit to 13-10. After both teams punted, the Patriots drove to the 49ers 41, but White couldn't get out of bounds in time after a 25-yard catch, and the Patriots led 13-10 at halftime. After the first four possessions of the second half ended in punts, the Patriots marched 80 yards in 10 plays, scoring on Brady's 5-yard connection to Amendola, increasing the lead to 20-10. Three possessions later, Brady found Mitchell for a 56-yard touchdown pass as Brady was falling down, capping off a 70-yard drive, upping the lead to 27-10. After a 49ers three-and-out, the Patriots kept pouring it on, driving all the way to the 49ers 20, and Gostkowski added a 38-yard field goal, widening the lead to 30-10. The Niners marched 75 yards on their next drive, scoring on Kaepernick's 13-yard touchdown pass to Shaun Draughn, trimming the deficit to 30-17. Amendola recovered the ensuing onside kick and the Patriots ran out the rest of the clock to end the game. The Patriots improved to 8-2. Running back LeGarrette Blount had a big day as he rushed for a total of 125 yards on 19 carries. In addition, Tom Brady also had a big day passing for a total of 4 touchdowns against the 49ers. This was also Brady's 199th career win (regular season and postseason combined), tied with Brett Favre for second place.

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