DENVER -- It was a wipe-out all right, just not the one expected by just about everyone outside the New York Giants.
Manning called it "a special win" for a reeling team that was without six starters a week after losing three wide receivers to season-ending injuries, including star Odell Beckham Jr.
Capping a stormy week of injuries and infighting, the Giants (1-5) pulled off one of the season's biggest upsets by dominating Denver in every phase from start to finish.
The Broncos (3-2), who are averaging just 14 points since their 42-17 rout of Dallas a month ago, blew a golden opportunity to close in on Kansas City in the AFC West after the Steelers knocked off the last unbeaten team in the league earlier Sunday.
"It's the National Football League," Denver's Von Miller said. "It's not about who you've got playing for you or what stars are in the game or what the team looks like. It's any given Sunday."
Visiting teams went 8-5 in Week 6 and are 46-44 overall this upside-down NFL season.
Jason Pierre-Paul had a trio of sacks for the Giants, who came into Denver tottering from a tumultuous week in which three wide receivers landed on injured reserve, five other starters were sidelined with injuries and cornerback Dominique Rodgers-Cromartie was suspended for insubordination.
"Nobody is giving us a chance in hell to win this ballgame," coach Ben McAdoo declared as he prepared to bring his team to Denver, where the Broncos were healthy, coming off a bye and leading the league in defense and swagger.
Yet the Giants had a goal-line stand to go with four sacks and two interceptions, double their season total. And it was the Broncos who bumbled their way through a nightmarish night filled with muffs and mistakes, flags and frustration.
"Our record wasn't good, but that doesn't mean we're a bad team," said McAdoo, who handed offensive play calling duties to coordinator Mike Sullivan for the first time. "We're a good football team."
So are the Broncos.
"Sometimes it just ain't your day," defensive end Derek Wolfe said, adding, "We didn't overlook this team. It wasn't like, `Oh, they're 0-5 and we're going to overlook them.' No, we were like, `These guys are a good team and we have to go out and play our best. We didn't play our best and that's why I'm (ticked)."
The sheer amount of sidelined starters actually worked in the Giants' favor.
"We didn't know what offensive linemen were playing, where they were playing, what receivers were playing," Wolfe said. "When you don't know who's playing, it's hard to game plan against them."
Quarterback Trevor Siemian was knocked out of the game briefly, and he lost his right tackle Menelik Watson (right calf) along with receivers Emmanuel Sanders and rookie Isaiah McKenzie to ankle injuries. Demaryius Thomas limped through a 10-catch night.
Before being soundly booed as they retreated to the locker room trailing 17-3 at the half, the Broncos kept hollering at each other in the huddle, couldn't convert third downs and gave up more big plays than they had all season.
The biggest came when Siemian, who earlier threw into triple and even quadruple coverage while overlooking open targets, threw a pick-six to cornerback Janoris Jenkins . His 43-yard interception return for a touchdown with 48 seconds left before halftime gave New York a two-touchdown cushion and left Siemian writhing in pain.
Siemian dived at Jenkins as he scooted past him near the goal line, and Siemian jammed his left shoulder into the ground. It's the same shoulder that bothered him almost all of last year and required surgery in January. He was replaced by Brock Osweiler but returned to start the second half.
"I tried to tackle the guy and that's certainly not my specialty," Siemian said. "I'm fine, a little sore, but I'm fine."
On this night, it was the Broncos who were the team in turmoil, falling behind 20-3 before Siemian hit Jeff Heuerman from 13 yards out with four minutes remaining.
KICKING WOES: Brandon McManus' miss from 35 yards out, his fourth missed chip shot of the season, was an ominous sign for Denver. He also had a 53-yard attempt that was blocked.
McManus has been anything but money since signing an $11.25 million extension last month. He's missed five field goals in 13 tries. Last year, he missed five times in 34 tries.
Coach Vance Joseph, however, said he won't be bringing in another kicker anytime soon.
"We'll address it with him," Joseph said. "But sitting here right now he's our guy."
BIG GAIN: The Broncos were allowing just 50.8 yards rushing per game. Orleans Darkwa gained almost that many on one run in the second quarter when he knifed right up the middle and wasn't pulled down until safety Justin Simmons caught up with him 47 yards later.
That set up Manning's 5-yard TD toss to tight end Evan Engram that gave New York a 10-0 lead.
Darkwa finished with 117 yards, the most this season against Denver.
The Broncos gained just 46 yards on the ground and C.J. Anderson failed to punch it in from the 1 even though it appeared he might have nudged the nose of the football over the goal line.
"For whatever reason," Siemian said, "we just didn't get it going collectively."
New York returns home to host the Seattle Seahawks before a bye week.
The Broncos visit the Los Angeles Chargers in the first of three consecutive road games.
For more NFL coverage: http://www.pro32.ap.org and http://www.twitter.com/AP-NFL
Follow Arnie Melendrez Stapleton on Twitter: http://twitter.com/arniestapleton
Josh McCown, who fractured his hand in the third quarter, showed just how much this season has meant to him during his postgame news conference.
Up to his old tricks, Tom Brady is yet again having an MVP-caliber season -- and impressing another 40-something QB in Vinny Testaverde.
Louis Riddick says he believes in Eagles' coach Doug Pederson's offensive mind and that the team should be able to play well under Nick Foles, but should even the run-pass balance.
With injured teammate Ryan Shazier on their minds, Ben Roethlisberger, Le'Veon Bell and Antonio Brown put up big numbers to propel the Steelers to a close victory against the Ravens.
Tom Brady and the Pats head to Miami where they have struggled in the Tom Brady era. Tune in Monday at 8:30 PM ET on ESPN to see if the Patriots will move to 11-2.
Ravens head coach John Harbaugh explains why he would rather not talk about how good the offense can be moving forward and rather just keep his focus on the team's next game.