Buffalo, who famously lost four consecutive Super Bowls in the early 1990s, have lethal passer Josh Allen at the helm of a dynamic offence that can strike fear into defences and have been tabbed as the early favourites to win it all this season.
The Bills also enter the campaign with a score to settle after a stunning overtime loss to the Kansas City Chiefs in last season's AFC Playoff Divisional Round where they scored a go-ahead touchdown with 13 seconds left in regulation.
The regular season follows what was one of the wildest NFL offseasons in recent memory and during which Super Bowl-winning quarterback Russell Wilson was among the nine players with a combined 39 Pro Bowl selections that were traded in March.
The addition of Wilson, who was acquired by Denver from the Seattle Seahawks, will give the Broncos plenty of optimism while battling in a loaded AFC West division that also includes the Chiefs, Las Vegas Raiders and Los Angeles Chargers.
"We've got a championship-caliber football team," Wilson said during training camp. "Now it's time to just show up and prove it, go out and do it."
The Chiefs' offense will have a different look given the departure of speedy receiver Tyreek Hill in a trade to Miami but quarterback Patrick Mahomes, one of the best at his position, and tight end Travis Kelce will continue to light up scoreboards.
In Tampa Bay, 45-year-old Brady will again lead the way for the Bucs after a short-lived retirement that lasted 39 days earlier this year and the team are a favourite to win a second Super Bowl in three seasons.
Brady missed the first two preseason games as he took time off for personal reasons but made a brief appearance during the third and final contest during which he looked sharp the one series he played and later declared himself ready to go.
"I feel good. I've played football for a long time. I'm pretty good at it," said Brady, who has won a record seven Super Bowl titles. "Doesn't take me long for me to remember how to play it."
Elsewhere in the league, the Cincinnati Bengals, who last season reached their first Super Bowl since 1989, have done well to fortify their offensive line to give better protection for quarterback Joe Burrow.
The Indianapolis Colts have some stability at quarterback after acquiring former NFL Most Valuable Player and four-times Pro Bowl selection Matt Ryan in a deal with the Atlanta Falcons.
In Pittsburgh, the Steelers begin a new era without Ben Roethlisberger as the two-time Super Bowl champion has retired and quarterback Mitch Trubisky will start the season in his place.
The Rams are looking to become the first repeat champions since the Brady-led New England Patriots did it in the 2003 and 2004 seasons but will have their work cut out for them in the parity-driven NFL.
