49ers vs. Bills odds, prediction, betting trends for NFL’s ‘Monday Night Football’ game

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When the 49ers (5-6) host the Bills (8-3) in Arizona in the penultimate game of NFL Week 13 on "Monday Night Football" (8:15 p.m. ET, ESPN), they will be looking to sneak back into the NFC wild-card race. The Bills will try to maintain their lead in the AFC East after both the Dolphins (8-4) and Patriots (6-6) won on Sunday.

The 49ers will be looking to keep pace with the Vikings and catch the Cardinals. They are coming off a huge win against the Rams in Week 12 and are getting healthier with running back Raheem Mostert, wide receivers Deebo Samuel and Brandon Aiyuk and cornerback Richard Sherman.

The Bills have gotten their offense going after a midseason slump and their defense is starting to play better, too. 

Here's everything to know about betting on 49ers vs. Bills in Week 13, including updated odds, trends and our expert's prediction for "Monday Night Football."

49ers vs. Bills odds for 'Monday Night Football'

  • Spread: 49ers by 1
  • Over/under: 47
  • Point spread odds: Bills -108, 49ers -112

The 49ers have been slight favorites throughout the week with some books having this game as a pick 'em. The Bills aren't the best road team and did lose to the Cardinals in Arizona on a Hail Mary. They return to State Farm Stadium while the 49ers are displaced from Santa Clara, Calif.

49ers vs. Bills all-time series

The teams have met only six times in their long histories and the 49ers have six wins and the Bills have six wins. The Bills dominated the 2016 meeting in Buffalo, 45-16. That was between the Jim Harbaugh and Kyle Shanahan eras. In 2012 with Harbaugh, the 49ers won 45-3. 

Three trends to know

— 51 percent of spread bettors like the Bills to pull off the victory in what's now a neutral site.

— 89 percent of over/under bettors think the total is too high and are taking the under because of the defenses.

— The Bills are 6-5 against the spread and 7 of their games have gone over. The 49ers are 5-6 against the spread and 5 of their games have gone over.

Three things to watch

The traveling 49ers

How will the 49ers adjust to their new home in the desert, also the home of their division rivals, the Cardinals? Shanahan should instill a strong mindset in an experienced, well-coached team that was able to win twice on trips to New York. There was no home-field advantage at Levi's Stadium with no crowds, anyway. They won't be affected as much as other younger teams might be.

Stefon Diggs vs. Richard Sherman

Diggs made a big play for a touchdown against the 49ers when playing for the Vikings in last year's divisional playoffs. But otherwise, Sherman and the 49ers' secondary contained him in a comfortable victory in route to Super Bowl 54. Diggs will get big-time coverage attention and was shut down last week against the Chargers. On the other side, Samuel and Aiyuk are tough to cover for the Bills because of their inside-outside versatility, quickness and toughness.

Josh Allen's health

The Bills' quarterback comes into the game with knee and ankle injuries he's playing through. That may limit what he can do athletically and in the supplemental running game as well as buying time to throw downfield against the 49ers' tricky defensive front. The Bills haven't been a great running team and will need him on point through the air to win, even with Nick Mullens as his counterpart.

Stat that matters

108.7. That's how many rushing yards per average the 49ers give up as a defense, 10th best in the NFL. Making the Bills one-dimensional should be helpful to go after Allen if they can contain Diggs downfield. The Bills are the No. 25 run defense facing the 49ers' running game which is now back on track with Mostert.

49ers vs. Bills prediction

The 49ers have some momementum and their offensive and defensive systems are saving them even with Mullens and other replacements. Between Shanahan and Robert Saleh, they will have the better overall game plans and can create the most matchup problems on both sides of the ball.  A less than 100 percent Allen is costly here.

49ers 27, Bills 24

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