Mahomes completed 19 of 29 passes for 236 yards and two scores in the 26-10 win Monday at Arrowhead Stadium. The Chiefs defense forced four turnovers, had two sacks and held the Patriots to 172 passing yards.
"When you are in dogfights like this and going against teams that are really good, whenever your number is called you have to make a play," Mahomes told reporters. "Guys made plays at the end of the game to give us enough points to get a win."
The Patriots played without Newton after he tested positive for COVID-19 last week. They used backup quarterbacks Brian Hoyer and Jarrett Stidham in place of their starting quarterback. Hoyer completed 15 of 24 passes for 130 yards and an interception before he was benched. Stidham completed 5 of 13 passes for 60 yards, a touchdown and two interceptions.
"I had two bad decisions that really cost us points," Hoyer said. "It's frustrating and disappointing, but I have to do a better job."
The game had been planned for Sunday, but was moved to Monday after each team reported a player with a positive test for COVID-19.
"We competed hard," Patriots manager Bill Belichick said. "We just didn't make enough plays."
Harrison Butker made two first-quarter field goals to give the Chiefs a 6-0 lead. Nick Folk made a 43-yard kick for the Patriots in the second quarter and the score was 6-3 at halftime.
The Patriots and Chiefs exchanged punts to start the third quarter before Taco Charlton sacked Hoyer and forced a fumble. The Chiefs recovered the fumble on their own 15-yard line. Mahomes then orchestrated a seven-play, 85-yard drive. He threw a six-yard score to Tyreek Hill to end the drive and give the Chiefs a 13-3 lead.
Stidham responded with a six-play, 59-yard scoring drive for the Patriots. He threw a four-yard touchdown pass to N'Keal Harry to end that drive.
The Chiefs scored on the next drive when Mahomes completed a six-yard touchdown pass to Mecole Hardman. Chiefs safety Tyrann Mathieu intercepted Stidham on the Patriots' next play and returned the interception for a 25-yard touchdown. The defensive score gave the Chiefs their final 16-point advantage.
Chiefs cornerback Rashad Fenton intercepted Stidham on the next drive.
"I thought we made plays when we had to make plays," Reid said. "We can learn from this. We have to do better in a lot of areas. It's tough to win in this league and tough to beat the Patriots in any situation."
The Chiefs (4-0) host the Las Vegas Raiders at 1 p.m. EDT Sunday at Arrowhead Stadium. The Patriots (2-2) battle the New England Patriots at 4:25 p.m. EDT Sunday at Gillette Stadium in Foxborough, Mass.