Payton, back on the sidelines after serving a season-long suspension for his role in the pay-for-pain 'Bounty-gate' scandal, reunited with quarterback Drew Brees, who connected on 26-of-35 pass attempts for 357 yards and a pair of touchdowns, as the Saints held on to clip division rivals the Atlanta Falcons 23-17.
In Buffalo, Stephen Gostkowski connected on a 35-yard field goal with five seconds left to lift Tom Brady and the Patriots to a heart-stopping 23-21 win over the feisty Bills while Russell Wilson tossed a 43-yard fourth-quarter touchdown to Jermaine Kearse as Seattle avoided a Week One upset, taming the Carolina Panthers 12-7.
The opening Sunday was filled with drama, as Nick Folk booted a 48-yard field goal with two seconds remaining as the New York Jets surprised the Tampa Bay Buccaneers giving rookie quarterback Geno Smith an 18-17 win in his NFL debut.
The Chicago Bears also offered new head coach Marc Trestman a victory in his debut beating the highly fancied Cincinnati Bengals 24-21 in another thriller.
The suspense carried over into the afternoon games with Greg Zuerlein hammering a 48-yard field goal with 40 seconds left on the clock to cap a fourth-quarter rally and give the St. Louis Rams a 27-24 victory over the Arizona Cardinals.
The wildest game of Week One, however, took place on the West Coast as the San Francisco 49ers battled to a 34-28 decision over the Green Bay Packers in a rematch of last season's divisional playoff clash.
Colin Kaepernick tossed a career high 412-yards and three touchdowns while Anquan Boldin pulled in 13 catches for 208 yards and one score in his Niners debut after coming over from the Super Bowl champion Baltimore Ravens.
In New Orleans, the Superdome was rocking as Payton was back prowling the sidelines for the first time in 20 months and the Saints were back to their winning ways after last year's disappointing and scandal-plagued season.
Brees fired touchdown strikes to Marques Colston and Jimmy Graham but it was the New Orleans defense that clinched victory when Roman Harper intercepted a Matt Ryan pass in the end zone with 43 seconds left to snuff out a last ditch Falcons drive.
"We kind of knew this game would be back and forth," said Payton. "We knew this could come down to the last possession.
"It's just important to get that first win and get the season started that way."
With favourite target Wes Welker signing with Denver and tight ends Rob Gronkowski out with injury and Aaron Hernandez in jail charged with murder, Brady was forced to work with an almost completely new cast of receivers and the lack of cohesion showed as the New England quarterback looked out-of-sync at times, completing 29-of-52 passes for 288 yards and two touchdowns.
Danny Amendola, brought into fill the hole left by Welker, looks like he could be Brady's new go-to-guy hauling in 10 passes for 104 yards while Julian Edelman had seven catches, including two touchdowns, helping the Patriots to a 10th straight opening day win.
The loss spoiled an impressive debut by Bills rookie quarterback E.J. Manuel, who began his NFL career by tossing a pair of touchdowns.
Minnesota and Detroit opened the season with an NFC North clash in the Motor City that featured the Lions' record smashing receiver Calvin Johnson and Vikings' NFL most valuable player running Adrian Peterson.
But it was Lions' Reggie Bush that stole the spotlight rushing for 90 yards and adding a touchdown and 101 yards on four catches to lead Detroit to a 34-24 win.
The game got off to an explosive start when Peterson, who came up nine yards short of the NFL single season rushing record last season, took his first handoff of the new campaign and raced 78 yards for the score.
Peterson would added another four-yard touchdown before the end of the half and collect a four-yard touchdown pass in the third quarter in a productive but losing effort.
The Kansas City Chiefs, who finished last season with a 2-14 record, got the new campaign off on the right foot thumping the toothless Jacksonville Jaguars 28-2.
Alex Smith, back in a starting role after being castoff by the San Francisco 49ers, threw two touchdown passes while the Chiefs' defense dominated, limiting the Jaguars to 178 yards total offense.
The Tennessee Titans pulled off a major upset, knocking off the Pittsburgh Steelers 16-9, while the Miami Dolphins beat the Cleveland Browns 23-10 and Andrew Luck tossed a pair of touchdowns and ran for another as the Indianapolis Colts put away the gritty Oakland Raiders 21-17.
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