Derrick Henry was a key player in the shock win. He rushed for 182 yards and a touchdown while Tennessee's defence kept Patriots great Tom Brady at bay.
The 42-year-old Brady's future in the game is uncertain. He said after the game that he wants to keep playing, but his contract with the Patriots is up.
Meanwhile Henry, celebrating his 26th birthday as well as the win, was thrilled with the outcome.
"It's a great win against a great team in a hostile environment," he told reporters after the game.
In Houston, the Texans beat the Buffalo Bills 22-19 in a game that went to overtime.
The hero for the home side was Deshaun Watson, who got away from a would-be sack and completed a pass that set up the winning field goal.
It was a stunning turnaround for Houston, who had trailed by 10 points in the second half.
"We never quit," Watson said in the post-game press conference. "Whatever it takes to get the win. I mean, we're going to keep fighting."