It's appearing more likely that Manning will have a former Patriots star receiver to help him.
Wes Welker is seemingly ready to go for his return to New England despite a concussion last week, and he'll look to help the Broncos notch a fourth straight win Sunday night.
While he's dealt with nagging injuries to both ankles, Manning is expected to face Brady for the 14th time. That includes three playoff matchups and a 31-21 defeat in New England on Oct. 7, 2012.
Denver (9-1) will seek to avenge that loss while continuing its momentum from a 27-17 victory over previously unbeaten AFC West rival Kansas City last Sunday. Manning threw for 323 yards and a touchdown in that win, and Montee Ball had a pair of scoring runs.
With 34 TD passes in 10 games, Manning remains on pace to reclaim the NFL single-season record from Brady. The Patriots quarterback had 50 touchdown passes in 2007, three years after Manning amassed 49.
The Broncos, though, didn't come away unscathed from their latest win, as their receiving corps seemingly took a big hit. Welker suffered a concussion and tight end Julius Thomas left with a knee injury, but both returned to practice Thursday.
While Thomas is questionable, Welker was cleared for full practice Friday and upgraded to probable for this game. Interim coach Jack Del Rio went as far as to say that if there was a 'definitely will go' category, Welker would be on it.
"I want to be out there," said Welker, who passed his baseline concussion test earlier in the week. "I mean, there are not too many games I've missed in my whole career and I love playing the game, especially in big atmospheres like this. So, I'm doing everything possible in my power to make sure that I get the opportunity to play in a game like this."
With 672 catches in his six seasons in New England, Welker was easily Brady's top target. He topped 1,000 yards in five of those campaigns and totaled 37 touchdowns before signing a two-year deal with Denver in March.
"(Welker is) a tough guy so he's played through everything," Brady said. "This is a big game for both teams so you have to expect their best players. I'm sure all those guys will be ready to go."
That toughness and experience have made Welker a primary target for Manning with 61 receptions for 648 yards, and he has helped Manning spread the wealth offensively as five Broncos players have at least 37 catches.
"He loves football. He's a tough guy. He plays through injuries," Manning said. "And those are things that you appreciate about a football player, especially playing in that slot position where he's taking a lot of hits."
The Broncos also placed safety Rahim Moore on recallable injured reserve Tuesday after he needed emergency surgery to stop bleeding in a left leg muscle. They signed Michael Huff, an eight-year veteran who was with Baltimore earlier this season, to take his place.
The Patriots, meanwhile, are coming off a controversial 24-20 loss at Carolina on Monday night. New England drove 62 yards in the final minute and seemed to catch a break when the Panthers were flagged after intercepting Brady's pass toward Rob Gronkowski in the end zone.
Officials instead waived off that pass interference penalty after deciding the ball was uncatchable, handing the Patriots the defeat.
Coach Bill Belichick and Brady were eager to put the controversy behind at the beginning of this week.
''It's not really our job to call the game. It's to play it and coach it. Whatever calls they make are the ones that we live with," Belichick said. "We have to turn the page here quickly, get on to Denver. Good football team, playing well. Obviously, their record reflects that."
While Denver is seeking to push ahead of Kansas City in its division, New England (7-3) will try to build on its two-game cushion in the AFC East. The Patriots have won three straight over the Broncos - including a 45-10 playoff rout Jan. 14, 2012, with Tim Tebow starting for Denver - and Brady is 9-4 in his lifetime matchups with Manning.
Brady connected with Welker on an 8-yard touchdown and ran for another in last season's win over Denver. Manning had 337 yards - and three TDs - to Brady's 223, but New England outrushed the Broncos 251-70 as Stevan Ridley had a career-high 151 yards.
Manning is 2-9 all-time on the road against New England, including the playoffs, and 2-7 in visits versus Brady.
"It's pretty well documented my respect for Tom as a quarterback," Manning said. "The way he prepares. The way he's better each season than the year before. Those are the couple of the many things that are impressive about him as a quarterback."
"Every time you play their football team, you're playing a well-coached, disciplined team."
Manning has topped 300 yards in his last three games versus the Patriots. He has thrown five interceptions during that streak but will face an injury-plagued defense this time.
Adrian Wilson, Jerod Mayo and Vince Wilfork are out for the season for New England, and defensive backs Alfonzo Dennard (knee) and Steve Gregory (thumb) missed last week's game. Cornerback Aqib Talib was forced to leave Monday's loss after aggravating a hip injury that caused him to miss the three previous games.
Brady has 12 touchdowns and one interception in his last five games against Denver. He tied an NFL playoff record with six TDs in the divisional round victory in 2012.