The Bills are 5.5-point favourites over the Texans with the over-under set at 44.5.
Houston will be rocking their all-reds, Buffalo their all-whites.
Now, let's get into who our experts picked before we break down the game!
Paul (100-48-1): Bills 24-14 Texans
Still no C.J. Stroud for Houston, who have seen Davis Mills play well, but also put up just 16 points against the Titans and barely beat the Jaguars.
Josh Allen is neither Cam Ward nor Trevor Lawrence, and will be one of Houston’s biggest challenges yet.
The Bills themselves haven’t been the best team across all three phases either, but I can’t see past the lopsided quarterback contest.
Give me Mitch Trubisky’s Bills!
Eric (96-52-1): Bills 20-16 Texans
The Texans' defence is nothing to scoff at. Sitting at No. 1 overall, they've allowed the second-fewest passing touchdowns (10), fifth-fewest rushing touchdowns (8), have forced the fourth-most turnovers (18), and are just one of three teams yet to allow more than more than 1,800 total yards of offence - one of the other two being the Bills, ironically enough.
Houston has allowed the fewest points (163) in the entire league - no other team has below 170 and only six teams are below 200.
Buffalo is 1-1 this season against teams with a top-10 defence - both games of which were decided by six points or less.
So I got the Bills riding the hot offensive hand here, but I think it will be closer than one would think.
Miguel (94-54-1): Bills 31-17 Texans
The Bills' potential is far superior to that of the Texans, and that should translate into a lopsided score in Buffalo's favor.
Having Josh Allen on offense should be enough for the Bills to beat the Texans, who are barely keeping up in their own division despite having the best defence in the NFL.
I'm going with the Bills by a wider margin than most.
Henri (86-62-1): Bills 24-17 Texans
This could be an entertaining matchup, as Houston has developed into having the best defence in the league.
The Texans excel particularly in rush defense and will certainly cause Allen, Cook, and company some problems.
Ultimately, Allen's Bills should prevail here, but it could be an exciting game with a few twists that will keep us well entertained.
Game breakdown
Houston has the No. 1 defence. Buffalo has the No. 2 offence. Both are slightly above average on their other sides.
Both teams are 3-1 in their last four games as each tries to gain ground in their own respective divisions.
In their past four games, the Texans have held opponents to 72 points in comparison to the Bills, who have allowed 75. But the offensive production is where the two begin to separate.
Houston has put up 93 points in the past four games, averaging a solid 367.5 yards (331.6 with David Mills at quarterback).
As for Buffalo, they've put up 125 points in the past four games - putting up at least 400 total yards of offence in three of them.
Bills quarterback Josh Allen is coming off an emphatic six-touchdown performance in the team's 44-32 win over the Tampa Bay Buccaneers last weeks.
He has now scored at least three touchdowns in six of the team's 10 games this season. But he has three interceptions in the past two games combined alone.
Funny enough, that's exactly how many turnovers Houston has forced in their past two games as well.
The Texans will continue to roll with Davis Mills at QB as CJ Stroud continues to recover from a concussion. Mills led the Texans on a game-winning drive against the Tennessee Titans - making it back-to-back weeks where he has led the Texans to game-winning drives.
Mills has now put up four touchdowns and just one interception with 566 passing yards on 53-of-86 passing (61.7% completion percentage).
Should the Texans pull off the upset, and the Jaguars lose to the Arizona Cardinals, they'll move up to second place in the AFC South and will take Jacksonville's Wild Card spot.
As for the Bills, they'll look to break their .500 record (2-2) on the road this season as they continue to fight an uphill battle for the top seed in the AFC.
Even with a win, they'll still sit behind the New England Patriots in the AFC East division.
Injury reports
LP = limited participant in practice / FP = full participant in practice / DNP = did not participate in practice
For Buffalo, wide receiver Mecole Hardman Jr., wide receiver Curtis Samuel, and tight end Dalton Kincaid are all inactive.
Defensive tackle Phidarian Mathis (LP) is questionable.
Over on Houston's side, safety Jalen Pitre (concussion) and Jamal Hill (hamstring), along with Stroud, are all inactive.
Everyone else on Houston is healthy and ready to go.