Heisman Trophy winner Robert Griffin III made a winning start to his NFL career with 320 yards passing and two touchdowns as the Washington Redskins beat the New Orleans Saints 40-32.
Griffin completed his first eight passes, including an 88-yard touchdown pass to Pierre Garcon, tying for the second-longest scoring pass by a quarterback making his NFL debut.
Rookie running back Alfred Morris rushed for 96 yards and two touchdowns. Aldrick Robinson, making his NFL debut, had a touchdown catch among four receptions for 52 yards.
Drew Brees uncharacteristically struggled with accuracy, completing only 46 percent of his throws with two interceptions. But his 339 yards passing and three TDs kept the Saints in the game until his last desperate pass was picked off by Reed Doughty near the Redskins' goal line.
"I've won a high school state championship and a bowl game in college, but to play in the NFL, the pinnacle of it all, and win your first game against a Hall of Famer in Drew Brees, it's at the top," Griffin said following the match.
"After the game, (Brees) told me he was proud of me. That's big for him to say after he just lost the game."
Brees quickly dismissed the idea that disruptions from the bounty probe, which resulted in a season-long suspension for coach and offensive mastermind Sean Payton, was to blame for New Orleans shaky start.
"We knew the type of team they were," he said.
"We knew the type of defence they were. They just came in and played better than we did, made fewer mistakes than we did, made more plays than we did."
Chicago's Jay Cutler threw for 333 yards and two touchdowns and Michael Bush added a pair of scoring runs to spoil Indianapolis quarterback Andrew Luck's debut with a 41-21 win for the Bears.
Brandon Marshall had nine catches for 119 yards and a touchdown in his first game since being reunited with Cutler, and Matt Forte ran for 80 yards and a score.
Luck finished his first NFL game 23 of 45 for 309 yards with a 4-yard touchdown pass to Donnie Avery early in the fourth quarter. He also was intercepted three times - twice by Tim Jennings - in an up-and-down effort as he steps in for the departed Peyton Manning.
Reggie Wayne caught nine passes for 135 yards. But it was a familiar result for a team with new management and a new coach in Chuck Pagano.
The New England Patriots recorded their ninth successive season-opening win with a routine 34-13 victory at the Tennessee Titans.
The Patriots, who lost the 2012 Super Bowl to the New York Giants, rode the reliable arm of Tom Brady, who threw for 236 yards and two touchdowns.
His opposing quarterback Jake Locker had a debut to forget after being sacked twice and conceding two turnovers.
Locker's miserable match came to an end when he hurt his shoulder in a tackle on Patrick Chung.
The New York Jets overpowered the Buffalo Bills 48-28 with quarterback Mark Sanchez prominent.
Sanchez threw three touchdown passes, including two to rookie Stephen Hill, Jeremy Kerley had a touchdown catch and a punt return for a score, and Antonio Cromartie took one of New York's three interceptions of Ryan Fitzpatrick to the end zone.
Tim Tebow found himself booed after one play on his debut for the Jets, as he failed to gain anything when he took off after taking a direct snap out of the shotgun late in the first half.
Tebow, on the field for just nine plays on offence, finished with 11 yards rushing on five carries and didn't throw a pass.
His biggest play came late in the game on special teams, when he recovered an onside kick in the fourth quarter and ended a late surge by the Bills.
Tampa Bay's rejuvenated defence came up with two interceptions against Cam Newton and the Buccaneers won their debut under coach Greg Schiano 16-10 over the Carolina Panthers.
Josh Freeman threw a 6-yard touchdown pass to Mike Williams and Connor Barth kicked three field goals to help the Bucs stop a 10-game losing streak that prompted the firing of former coach Raheem Morris. Schiano came the Tampa after spent the past 11 seasons transforming Rutgers from one of the losingest programs in college football into a Big East contender.
Newton threw for 303 yards and one touchdown.
Rookie quarterback Ryan Tannehill suffered on his debut as the Miami Dolphins slumped to a 30-10 defeat to the Houston Texans.
The Texans' defence had too much know-how for Tannehill, who started well before throwing three interceptions in a six-minute spell late in the first half which changed the complexion of the game.
For Houston, Arian Foster had two touchdown runs and Matt Schaub threw a TD pass to Andre Johnson.
Michael Vick overcame four interceptions as the Philadelphia Eagles edged past the Cleveland Browns 17-16.
Vick was a long way from his best but was still the match-winner when he threw a four-yard touchdown pass to Clay Harbor with 1:18 left in the fourth quarter.
Vick went 29 of 56 for 317 yards and two TDs, his first going to Jeremy Maclin.
Adrian Peterson scored two touchdowns for the Minnesota Vikings in their 26-23 overtime victory over the Jacksonville Jaguars.
As impressive as Peterson was, the Vikings were still indebted to Blair Walsh, who kicked four field goals, including a 55-yarder as regulation expired and another in overtime.
San Francisco's defence smothered Aaron Rodgers and the Green Bay offence for most of the game, then made one last stand to stop a late rally as the 49ers ran out 30-22 winners.
The Packers rallied from a 16-point deficit in the fourth quarter, and pulled within eight points when Aaron Rodgers threw a touchdown pass to James Jones with 6:05 left, but the 49ers defence held the Packers in the final minute to come away with a big win to open the season.
Randall Cobb's 75-yard punt return for a touchdown and a 2-point conversion early in the fourth quarter cut the 49ers lead to 23-15. But Rodgers threw an interception to linebacker NaVorro Bowman and Frank Gore ran for a 23-yard touchdown.
David Akers tied an NFL record when he kicked a 63-yard field goal to the end the first half, with the ball bouncing off the crossbar and going through the uprights.
A late rally by the Seahawks was not enough to claim victory in Glendale as Seattle went down 20-16 to the Arizona Cardinals.
Kevin Kolb replaced injured John Skelton and led Arizona on the deciding touchdown drive, throwing 6 yards to Andre Roberts for a score with 4:59 to play.
Aided by two pass interference penalties, Seattle drove to the Arizona 4 in the final seconds. But rookie Russell Wilson threw three straight incompletions and the Cardinals held on.
Adding to the confusion, Seattle appeared to have called a timeout when it had none remaining, but that turned out to be a mistake by the replacement officials working the game.
Peyton Manning enjoyed a successful Denver debut on his return to NFL action after a 20-month absence as the Broncos opened their season with a 31-19 victory over the Pittsburgh Steelers.
The 36-year-old four-time MVP, who missed the entire 2011 campaign for Indianapolis after undergoing spinal fusion surgery, completed 19-of-26 passes for 253 yards and two touchdowns.
His first score for his new team - a 71-yard toss to Demaryius Thomas - was his 400th career touchdown pass.
In the other afternoon games, Matthew Stafford threw a five-yard touchdown pass to Kevin Smith with 10 seconds left to give the Detroit Lions a 27-23 win over the St Louis Rams while Matt Ryan threw for 299 yards and three touchdowns as the Atlanta Falcons overcame the Kansas City Chiefs 40-24.