Drew Brees set an NFL touchdown record on the way to helping the New Orleans Saints record a first victory of the season with a 31-24 triumph over the visiting San Diego Chargers.
Brees connected on a 40-yard effort in the first quarter to give him 48 straight games with a touchdown pass, taking him one clear of the mark set by Johnny Unitas in 1960, before he rallied his team for an overdue victory.
After establishing the new record, Brees dug New Orleans out of a 24-14 hole to help the Saints end a run of four consecutive defeats in front of a relieved home crowd that included banned head coach Sean Payton, who was allowed to attend the game.
Payton has been suspended for the entire season due to his alleged involvement in the New Orleans Saints bounty scandal.
Brees finished with 370 yards passing and four touchdown throws, including three to Marques Colston, who added 131 yards receiving for the 1-4 Saints.
San Diego quarterback Philip Rivers threw for 354 yards and two scores, but his attempt to tie the game in the final seconds stalled in New Orleans territory when he was sacked by Martez Wilson, who forced a fumble and recovered possession.
Andrew Luck and Reggie Wayne teamed up to wipe out an 18-point half-time deficit and give Indianapolis Colts a stunning 30-27 win over Green Bay Packers.
It had been a tough week for the Colts, who revealed on Monday that head coach Chuck Pagano was in hospital after being diagnosed with leukaemia, but rookie quarterback Andrew Luck showed his class in rallying his team to an inspiring win.
Luck, the first pick in April's NFL Draft, put his team ahead with 35 seconds remaining after finding Reggie Wayne with a four-yard pass to cap a 13-play, 80-yard drive that brought unavoidable comparisons with his predecessor Peyton Manning.
"This did mean a whole lot with how the week went," said Wayne. "I talked to coach Pagano and he wanted us to win so bad. This was for Chuck."
As Manning did so often, Luck made full use of receiver Wayne, who he found 13 times for 212 yards, including five times on the decisive drive.
The Packers, who began the season among the favourites to win the Super Bowl but have stumbled to a 2-3 record, missed a potential game-tying 51-yard field goal with three seconds to play.
Matt Ryan helped the Atlanta Falcons to a 24-17 victory over Washington Redskins, guaranteeing the Falcons a first-ever 5-0 start in their franchise history.
Michael Turner ran 13 yards for the go-ahead score with less than three minutes remaining, with Ryan completing 34 of his 52 passes to earn Atlanta the win.
It was an eighth consecutive home loss for the Redskins, with Heisman Trophy winner Robert Griffin III having to leave the field with concussion.
Shaun Suisham kicked a last-gasp 34-yard field goal to guide the Pittsburgh Steelers to a 16-14 triumph over the Philadelphia Eagles.
The Eagles took the lead on a two-yard touchdown pass from Michael Vick to Brent Celek with less than seven minutes remaining, but the Steelers responded by driving 64 yards to set up the winning kick, including a pair of key third-down conversions by quarterback Ben Roethlisberger.
The Miami Dolphins avoided last-minute heartbreak as Reshad Jones picked off Andy Dalton's overthrown pass to preserve a 17-13 victory over the Cincinnati Bengals, ending two weeks of miserable finishes.
Elsewhere, Justin Tucker made all three of his field goal attempts as the Baltimore Ravens kept the Kansas City Chiefs out of their end zone to preserve a 9-6 victory.
Russell Wilson and the Seattle Seahawks defence were too much for the Carolina Panthers to overcome.
Wilson threw a 13-yard touchdown pass to Golden Tate with 35 seconds left in the third quarter to help the Seahawks beat the Panthers 16-12.
The defending Super Bowl champion New York Giants rallied from a 14-0 first-quarter deficit to beat the winless Cleveland Browns 41-27.
Receiver Victor Cruz scored three touchdowns while running back Ahmad Bradshaw rushed for a career-high 200 yards and one score in the home victory.
The San Francisco 49ers dominated the Buffalo Bills 45-3 and put up 621 yards of total offence with quarterback Alex Smith throwing for three touchdowns and 303 yards.
Another team with just one loss is the Chicago Bears, who had little trouble registering a 41-3 road win against a poor Jacksonville Jaguars squad.
The NFL's surprise team at 4-1 is the Minnesota Vikings whose impressive early season form continued with a 30-7 win over the Tennessee Titans.
Percy Harvin had 108 yards receiving for the Vikings scoring one rushing and one receiving touchdown.