Tom Brady threw his 400th touchdown pass as the New England Patriots enjoyed a 51-17 rout of the Jacksonville Jaguars.
Brady may have begun the season under a cloud of controversy following 'deflategate' but was busy doing what he does best on Sunday as he completed 33 of 42 passes for 358 yards and connected with Danny Amendola and Keshawn Martin for a couple of touchdown passes.
LeGarrette Blount scored three on the ground while Rob Gronkowski caught four passes for 101 yards.
The Pittsburgh Steelers gutted out a 12-6 win over the St Louis Rams but it came at a cost as quarterback Ben Roethlisberger left the game early with a knee injury.
Le'Veon Bell, back from suspension, scored a touchdown with a one-yard run in the first quarter and it proved enough as the Steelers defence stood firm.
The game was delayed after a firework display led to a section of turf catching fire, but that is as explosive as things got for the Rams, who were held to a two field goals from Greg Zuerlein.
The Dallas Cowboys looked a little lost without Tony Romo and Dez Bryant as the fell to a 39-28 defeat to the Atlanta Falcons.
Matt Ryan threw two touchdown passes to Julio Jones while Devonta Freeman rushed for 141 yards and three scores.
The Cowboys had won six in a row in regular-season play but fall to 2-1 this year with the loss.
Adrian Peterson appeared to be back to his best as he rushed for 126 yards and two touchdowns in three quarters to help the Minnesota Vikings beat the San Diego Chargers 31-14.
They were the first scores of the season for Peterson, who played only one game in 2014 due to suspension.
Cam Newton threw for 315 yards and two touchdowns while also adding a touchdown on the ground as the Carolina Panthers beat the New Orleans Saints 27-22.
Luke McCown, starting at quarterback for the Saints in place of the injured Drew Brees, completed 31 of 38 passes for 310 yards but the Saints were undone as they twice went for two-point conversions and twice failed, leaving them chasing a touchdown on their final drive instead of a field goal to tie it.
Panthers cornerback Josh Norman essentially sealed the win by picking off McCown in the end zone with 69 seconds left.
Andrew Luck had a pair of touchdown passes in the space of a minute in the fourth quarter as the Indianapolis Colts rallied to stun the Tennessee Titans 35-33.
Luck capped a 98-yard drive with a 35-yard touchdown pass to Phillip Dorsett with 6:49 to go, and after Dwight Lowery picked off Titans rookie Marcus Mariota, Luck found Donte Moncrief from 11 yards 56 seconds later.
Derrick Carr had a pair of touchdown passes and Latavius Murray collected 139 yards and a pair of scores on the ground as the Oakland Raiders beat the Cleveland Browns 27-20, ending an 11-game losing streak on the road.
The Philadelphia Eagles won their first game of the season as they held on to beat the New York Jets 24-17 despite the absence of the injured DeMarco Murray.
Darren Sproles had two touchdowns, including an 89-yard punt return.
Ryan Mallett threw for 228 yards and a touchdown as the Houston Texans beat the Tampa Bay Buccaneers 19-9.
Andy Dalton threw for 383 yards and three touchdowns to lead the Cincinnati Bengals to a 28-24 win over the Baltimore Ravens.
