Reigning NFL MVP Tom Brady threw three touchdown passes as New England Patriots opened the season with a 27-20 win over Houston Texans.
Brady connected three times before half-time to give last season's losing Super Bowl finalists a 21-6 advantage at the interval with Rob Gronkowski finishing with seven catches for 123 yards, including a touchdown.
Cleveland Browns are still searching for their first win since 2016 after opening up with a tie against Pittsburgh Steelers.
However, they would have broken their winless run had Zane Gonzalez not had his field goal attempt blocked on the final play of over-time with the scores locked at 21-21.
Quarterback Ryan Fitzpatrick starred with a 417-yard four touchdown performance as Tampa Bay Buccaneers beat New Orleans Saints 48-40.
Baltimore Ravens were 47-3 winners over the Buffalo Bills, with the Jacksonville Jaguars edging out NY Giants 20-15.
Minnesota Vikings debutant Kirk Cousins passed for two touchdowns, with his side forcing four turnovers, in a 24-16 victory over San Francisco to inflict 49ers' quarterback Jimmy Garoppolo's first defeat in eight games as a starter.
Cincinnati Bengals were not duly affected by safety Shawn Williams' ejection just 30 minutes into their 34-23 win over Indianapolis Colts.
Williams was the first player to transgress the new rule over the use of the helmet after his late hit on Colts' quarterback Andrew Luck.
Later, the Miami Dolphins overcame the Tennessee Titans 27-20 after two weather delays, with the game taking seven hours and 10 minutes overall to complete, Jakeem Grant breaking the tie with 14 minutes remaining.
New Redskins quarterback Alex Smith led Washington to a 24-6 win over the Arizona Cardinals, throwing for 255 yards and two touchdowns, while Cam Newton threw for 58 yards and one touchdown in the Carolina Panthers' 16-8 victory over the Dallas Cowboys.
The Green Bay Packers rallied from a 20-point deficit to edge out the Chicago Bears 24-23, Aaron Rodgers returning from a knee injury in the first half for the go-ahead touchdown with just over two minutes left on the clock.
Patrick Mahomes became the Kansas City Chiefs' third ever player to throw for four touchdowns in an opening game, lifting the Chiefs to a 38-28 win.
Elsewhere, debutant Case Keenum had a night of mixed fortunes, throwing three interceptions and three touchdowns in the Denver Broncos' 27-24 victory over the Seattle Seahawks.
