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.
The game began with a coin toss in which the Patriots won and elected to kick. The 49ers began with a touchback starting at their own 25. During this drive, 49ers' quarterback Colin Kaepernick was sacked twice. The first time by cornerback Malcolm Butler and the second time by safety Patrick Chung. Being at a 4th and 21, the 49ers punted with Bradley Pinion. Danny Amendola received the punt at the Patriots' 43 and ran it back 30 to the 49ers' 27 being tackled by Blake Bell. The Patriots started their first drive of the game very well, capping it off with a Julian Edelman 4-yard pass from Brady. Unfortunately for the Patriots, Stephen Gostkowski missed the PAT-attempt. The 49ers obtained the ball once again beginning at their own 25. During this drive, the 49ers fumbled twice. However, both fumbles were recovered by the 49ers. They also acquired 3 points with Phil Dawson's 33-yard field goal. Nonetheless, on the very next Patriots' drive, they managed to get a touchdown. Beginning the drive very well with a LeGarrette Blount 44-yard run which moved the Patriots to the 49ers' 33, they ended it with a James White 9-yard pass from Brady. Unlike the Patriots, the 49ers were not able to get a touchdown put rather punted on their next drive. Kaepernick was sacked by linebacker Kyle Van Noy. The Patriots began their possession at their 29. Differently from before, the Patriots were unable to generate any points on this drive but rather punted. The 49ers received the ball at their own 8-yard line. The managed to move the ball all the way to the end zone. Finishing the drive, with a Vance McDonald 18-yard touchdown reception. The next Patriots' drive ended in disaster beginning with a penalty on offensive lineman Nate Solder that moved them back 5-yards and then a sack on Brady by Ahmad Brooks which force a 4th and 22. The Patriots punted giving the ball at the 49ers' 39. Similarly to the Patriots, the 49ers were also unable to get a first down. Amendola muffed the punt, nearly losing the ball to the 49ers. The Patriots tried to make some points out of their possession but with only 1:11 left in the first half. Reaching the 49ers' 41, they were unable to achieve this.
Starting the second half, the Patriots began with the ball. Unfortunately, they went three and out unable to get a first down. During their punt, Jeremy Kerley muffed the ball but it went out-of-bounds. During this drive, the 49ers punted only being able to reach their own 39. The Patriots received the ball at their own 18. On 5th play of this drive Brady was sacked and fumbled the ball, Ahmad Brooks recovered it. However, this call was turned back with a defensive-holding call on Rashard Robinson. Unluckily, the Patriots were forced to punt again giving a touchback to the 49ers. Like the Patriots, the 49ers were also punt. On their 4th play of the drive, center Daniel Kilgore fumbled but Kaepernick recovered the ball. The score was still 13–10 after 7 total drives. The Patriots began at their own 30. They were able to reach the 49ers' end zone on an Amendola 5-yard pass. The drive occurred in 10 plays, 4:21 going for a total of 80 yards. The following 3 drives would all end in punts. The first one of the three occurred with the 49ers going 3 and out. The second would include the Patriots going out with a similar fashion as the 49ers. And the following 49ers' drive would also include them going three and out. On the next Patriots possession they began at their own 30. On the last play of this drive, Brady was able to scramble out of the pocket throwing 55-yard catch and run pass to wide receiver Malcolm Mitchell. This was Mitchell's first touchdown in his entire career. The incoming 49ers' drive would end in a punt. While, the following Patriots' drive would end in a Gostkowski 38-yard field goal. After this, the 49ers gained possession again and managed to score a meaningless touchdown in a Shaun Draughn touchdown pass from Kaepernick. The Patriots finished the game with a Tom Brady kneel, finishing the game with a score of 30–17.
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.