Against their rival Dolphins, the Patriots raced out to an early domination. After taking the opening kick-off, the Patriots stormed 75 yards in just 8 plays scoring on quarterback Jimmy Garoppolo's 12-yard touchdown pass to wide receiver Danny Amendola for an early 7–0 lead. After a Dolphins three-and-out, the Patriots raced 75-yards in just 7 plays, on a nearly identical drive, and Garroppolo found tight end Martellus Bennett on a 20-yard touchdown pass for a 14–0 lead just eight-and-a-half minutes into the game. After another Dolphins failed to move the ball again, the Patriots marched 76-yards in over 6 minutes with another Amendola touchdown catch extending the Patriots lead to 21–0 a few plays into the second quarter. This would be his second touchdown catch. After a series of punts the Patriots reached their 43, but Amendola fumbled at the Dolphins 42 after a 15-yard reception and linebacker Kiko Alonso recovered at the Dolphins 42. However, two plays later wide receiver Jarvis Landry lost a fumble with defensive end Chris Long recovering at the Patriots 48. On the fifth play of the drive, Garoppolo was driven to the ground by Alonso on a completion to wide receiver Malcolm Mitchell and Garoppolo suffered a shoulder injury that required transportation to Massachusetts General Hospital; he finished with 232 yards and three touchdowns. Rookie quarterback Jacoby Brissett took over and running back LeGarrette Blount drove the Patriots to the Dolphins 16 and placekicker Stephen Gostkowski finished the drive with a 34-yard field goal for a 24–0 lead. Four plays into the Dolphins next possession, Jamie Collins intercepted quarterback Ryan Tannehill and returned it 13-yards to the Dolphins 49. However, the Dolphins defense forced the Patriots to go three-and-out and the Dolphins finally got on the board, storming 77-yards in just under a minute and placekicker Andrew Franks' got the Dolphins on the board with a 27-yard field goal just before halftime.
The Dolphins stormed out of the gate in the second half, reaching the Patriots 34, but running back Jay Ajayi fumbled and linebacker Jonathan Freeny recovered for the Patriots. The Patriots took advantage by racing 68-yards in just 5 plays to score on Blount's 9-yard touchdown run which seemingly put the game away with a 31–3 score fairly early in the third quarter. The Dolphins responded with their 75-yard drive being capped off with Tannehill bombing a 24-yard touchdown pass to wide receiver Kenny Stills, trimming the deficit to 31–10. After a Patriots three-and-out, the Dolphins stormed 88-yards in just 5 plays. At the Patriots 32, cornerback Logan Ryan was flagged for pass interference, moving the ball to the Patriots 12. On the very next play, Tannehill found tight end Jordan Cameron on a 12-yard touchdown pass, making the score 31–17 early in the fourth quarter and pulling the Dolphins back into the game. The Patriots drove to the Dolphins 35 on their next possession, but a penalty and near lost fumble forced the Patriots to punt. The Dolphins then stormed 74-yards, scoring on rookie running back Kenyan Drake's 7-yard touchdown run melting the Patriots once four-touchdown lead to just one with 6:06 remaining in the game. The Patriots drove all the way to the Dolphins 21, but Gostkowski missed the 39-yard field goal wide right with 1:04 remaining, that would've put the game away, keeping the Dolphins hopes alive. The Dolphins stormed to the Patriots 29, but Tannehill was intercepted by safety Duron Harmon in the endzone with 0:02 left to seal the win for the Patriots.
With the win, the Patriots improved to a record of 2–0. Tannehill threw for 387-yards, but his two interceptions and Ajayi's fumble proved to be costly. Brissett completed 6 of 9 passes for 92-yards. LeGarrette Blount ran for 123-yards and a touchdown. After the game it was learned Garroppolo would miss 4–6 weeks and Brissett would start the next two games.