This is a dangerous game for the Bills against a 49ers team that is undefeated when playing as a home team in Arizona. San Francisco's strength on the ground matches up well against Buffalo's defensive weakness, and this should be the first time since Week 6 that Deebo Samuel, Brandon Aiyuk and Raheem Mostert play together. In the writing of this blurb, I almost convinced myself to pick the 49ers against my better judgment.
Buffalo Bills 27, San Francisco 49ers 26
MDS's take: I admire how hard the 49ers are playing in tough circumstances, but the Bills won't have much trouble beating this injury-plagued roster.
MDS's pick: Bills 23, 49ers
Florio's take: The 49ers have a complex and diverse running game. The Bills have a hard time stopping the run. San Francisco continues its unlikely run to a playoff berth, where the 49ers will be very dangerous if they make it.
Florio's pick: 49ers 21, Bills 20
The San Francisco 49ers appear to have the Rams' number. Despite the fact their roster has been ravaged by injuries, the Niners just beat the Rams for the second time in a seven-week span. That's likely why they're only getting 1.5 points at a neutral site against the contending Buffalo Bills on Monday night.
The majority of our experts are under the impression that's a dynamic Bills backers can take advantage of.
Against teams not named the Rams who have winning records this season, the 49ers are 0-5 straight-up and against the spread with an average margin of loss of 14.2 points.
"The Bills have to be the NFL's quietest and maybe most disrespected division leader," Miller said. "That's the only way to explain a 1.5-point spread against the San Francisco—or is it Glendale now?—49ers. The Niners are still without George Kittle and Nick Bosa, right? Brandon Aiyuk alone isn't worth believing the 49ers can suddenly keep pace with the Buffalo offense or move the ball consistently on the Bills defense."
Still, Buffalo has laid some eggs against veteran teams this season and this is, again, far from unanimous.
Prediction: Bills 27, 49ers 23
This game will be played at the Cardinals stadium because of Covid issues, which means it's the second time Buffalo will have played in the stadium. They lost on a Hail Mary to the Cardinals earlier this year. San Francisco is coming off an impressive road victory against the Rams, but this Bills team is better than the Rams on offense. That will show up. Bills take it.
Pick: Bills 26, 49ers 20
The 49ers have a couple key pieces back in Raheem Mostert and Deebo Samuel, and the defense is good enough to challenge Josh Allen — who has a few more turnovers last two weeks. The Bills are 3-2 on the road this year, but this is one of those tough outs.
Pick: 49ers 24, Bills 21
The 49ers (5-6) got running back Raheem Mostert and cornerback Richard Sherman back from injuries last weekend and proceeded to give the Rams their first loss at SoFi Stadium. This matchup is even more difficult because San Francisco must get used to its temporary home at the Cardinals' State Farm Stadium while hosting the Bills (8-3), a solid playoff contender that on a good day is extremely effective on both sides of the ball. Buffalo is favored for a reason, but the 49ers seemed to enjoy the role of spoiler last week, and they will undoubtedly be looking for a repeat.