The Bills are 5.5 favorites at most sportsbooks heading into Sunday's game against the Jacksonville Jaguars in London's Tottenham Stadium.
Check out game predictions from national analysts.
For the first time ever, a team is playing two straight games in London. Will it be a factor? We'll find out.
Florio: Bills, 28-20.
Simms: Bills, 24-20.
This is Buffalo's home game, but the Jaguars will have been in London for over a week by the time this kicks off. That's an edge. Buffalo was dominant last week against Miami, and Josh Allen is playing at a high level. The Jaguars looked better last week, but they won't be able to slow Allen. It will be high scoring. Bills win it.
Pick: Bills 30, Jaguars 20
I have concerns about this Jaguars team. They have an uncanny ability to make third-and-1 feel like third-and-27. Jacksonville feels like a group that's overthinking it right now. They need a little more "Why don't we let our supremely gifted quarterback do his thing?" in their offense. I thought the Jaguars had a chance to be a top-five offense this season. Through four weeks, they rank 25th in expected points added per drive.
Meanwhile, last week against the Dolphins, we saw a near-perfect version of quarterback Josh Allen. He made the layups against the Dolphins but still used his physical gifts to make the 1 percent second-reaction plays. The Bills scored touchdowns on four of their first five possessions en route to a 48-20 victory.
I generally like Jaguars coach Doug Pederson in an underdog role, but his team seems a bit stuck right now offensively, and the Bills are rolling.
The pick: Bills (-5.5)
Josh Allen is red-hot defensively for the Jaguars coming off a three-sack game against the Falcons. Josh Allen is red-hot offensively for the Bills, coming off a perfect passer rating with five total scores against the Dolphins. The Jaguars' Josh owned the Bills' Josh in a shocking upset two seasons ago. Jacksonville game in this rematch, too, after winning in London last week and staying there. Trevor Lawrence will grind through vs. the Bills' defense to make big plays and get his team in position to win late.
Pick: Jaguars win 26-24.
The Bills held their first and only practice in England prior to Sunday's game against Jacksonville.
Storyline to watch: While it's a Bills "home" game, the Jaguars are on the second of back-to-back weeks in London, which means Jacksonville has the time zone experience advantage. But the Jaguars will be challenged to slow down a Bills offense that's averaging 5.9 yards per play (fourth) while the Jaguars' defense is allowing 5.4 yards per play (22nd). -- Alaina Getzenberg
Bold prediction: QB Josh Allen will score a touchdown, and so will ... LB Josh Allen. Not a big deal if Buffalo's Allen runs for a TD -- he has 40 over his career, including two this year -- but Jacksonville's Allen has just one TD in his five-year career: a 37-yard fumble return that gave the Jaguars a 20-16 victory over Tennessee in Week 18 last season. -- Mike DiRocco
Stat to know: QB Allen had four touchdown passes last week, the 10th such game in his career. He is tied with Jim Kelly for the most in Bills franchise history. The last quarterback to throw four TD passes in consecutive games was Joe Burrow in Weeks 16-17 in 2021.
Matchup X factor: Jaguars cornerbacks Tyson Campbell and Darious Williams. Jacksonville has a strong run defense, and if these two corners -- who both have allowed lower than average yards per coverage snap this season, according to NFL Next Gen Stats -- can slow down the Bills' passing attack, the Jaguars have a chance. -- Walder
Betting nugget: Doug Pederson is 32-23 against the spread (ATS) in his career as an underdog, including playoffs. He is 9-6 ATS as an underdog to the Bills.
Moody's pick: Bills 31, Jaguars 24
Walder's pick: Bills 33, Jaguars 20
FPI prediction: BUF, 79.5% (by an average of 11.3 points)
I believe the Jaguars have a bigger home-field advantage in London than they do in Jacksonville. They can navigate the unusual travel much better having done it so often. The Jaguars are in London for a second straight week. And despite all of those edges, they're facing a Bills team that has won its last three games by 28, 34 and 28 points. And I'm still not too impressed with anything I've seen from the Jaguars.
Bills (-5.5) over Jaguars
"The Bills should be heavily favored over the Jaguars after their performance against the Miami Dolphins," Sobleski wrote. "As a straight-up pick, Buffalo is an easy choice. However, Jacksonville holds a significant advantage this week to keep the contest close.
"The Jaguars played in London this past weekend as part of this season's first international game. With back-to-back games in Merry Old England, the team chose to stay and practice overseas all week. The Jags already adjusted to the time difference with no extra travel. The Bills don't have the same luxury."
ATS Consensus: Bills -5.5
SU Consensus: Bills
Score Prediction: Bills 31, Jaguars 21
The Buffalo Bills have dominated three opponents in a row, including a 28-point win against the dangerous Miami Dolphins. Now, they'll cross an ocean to face the Jacksonville Jaguars.
Jacksonville beat Atlanta in London last week, so it won't have to deal with the unordinary travel like the Bills. It's hard to quantify how big of an edge that is, as this is the first time an NFL team will play two games in the same season overseas.
Despite that wrinkle, Josh Allen is the current MVP favorite, and the Bills' defense has been among the league's best. Trevor Lawrence and the Jaguars have struggled early, but they have the raw materials to scare any team.
Score Prediction: Bills 26, Jaguars 23
Why Brooke is taking the Bills: The Bills' defense has been lights out the last few weeks, holding the explosive Dolphins to their lowest point total of the season. While the loss of Tre'Davious White is a concern, Buffalo still has enough playmakers on that side of the ball to prevent Trevor Lawrence and Co. from going toe to toe with its own Josh Allen-led unit, which has averaged 38.7 points per game since Week 2. You could make the argument that the Bills are the best team in the NFL heading into Week 5, but the thing that makes this a closer game than one might think is the neutral location and the fact that Jacksonville has been in London for an extra week.