Week 10 NFL Predictions: Will the Broncos Shock the Struggling Bills on Monday Night Football?
After winning two games in a row before their Week 9 bye, the Denver Broncos are well-rested and are considered one of our top NFL upset picks for Week 10. When making our NFL picks, we always search for the best odds from our top sports betting apps.
The Buffalo Bills have hit a rough patch after a strong 3-0 start, where they dominated opponents with a 123-33 scoring margin from Weeks 2 to 4. The team’s record has slipped to 5-4 after a 24-18 loss to the Cincinnati Bengals last week, leading to a decrease in their NFL playoff odds due to their recent struggles.
Although Buffalo has faced challenges, the Bills are expected to make a strong comeback. However, the Broncos, who have been on a winning streak with victories over top teams like the Kansas City Chiefs, are not to be underestimated. The upcoming game between the Bills and the Broncos is sure to be exciting, as Buffalo aims to show their strength at home while Denver hopes to continue their winning streak, making it a highly anticipated and closely watched matchup.
Take a look at our NFL Week 10 predictions, Week 10 NFL props, and top NFL upset picks for Week 10. Odds are provided by our recommended NFL betting sites, and pick confidence is rated on a 1-5 star scale.
Week 10 NFL Upset Predictions
- Cleveland Browns are the underdogs at +230 odds according to FanDuel, facing off against the Baltimore Ravens. This game is rated four stars.
- Jacksonville Jaguars are the underdogs with +140 odds according to Caesars, as they face off against the San Francisco 49ers with a four-star rating.
- The Denver Broncos are underdogs at +320 odds through FanDuel in their matchup against the Buffalo Bills. This game is rated three stars.
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NFL upset predictions
The Cleveland Browns are the underdogs with odds of +230 via FanDuel, facing off against the Baltimore Ravens. This game is rated with four stars.
Even without Deshaun Watson for most of the season, the Cleveland Browns have remained competitive in the AFC North, trailing the first-place Baltimore Ravens by just two games as they head into Week 10. The Browns’ defense has been stellar, shutting down the Arizona Cardinals to only 58 total yards in a dominant 27-0 victory last week. Watson, who is showing signs of recovering from injury, had an impressive performance with 219 passing yards, two touchdowns, and no interceptions in that game.
Lamar Jackson and the Ravens continue to dominate, defeating the Seattle Seahawks 37-3 last week for their fifth win in six games. Despite their recent success, Baltimore has struggled with occasional setbacks, including a home loss to the Indianapolis Colts in Week 3 and a 17-10 defeat to the Pittsburgh Steelers two weeks later.
In their early October matchup, Baltimore dominated the Browns with a score of 28-3. However, Watson was unexpectedly unable to play, leading Cleveland to start Dorian Thompson-Robinson at quarterback for the first time in his career. Despite this, the Browns had a strong history of covering the spread in their previous games against the Ravens and had not lost by more than a touchdown in their last five meetings with Baltimore.
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The Jacksonville Jaguars are the underdogs at +140 against the San Francisco 49ers ⭐⭐⭐⭐ according to Caesars sportsbook.
It is rare to see a road team favored over a team with a better record, but that is the situation this week with the 6-2 Jacksonville Jaguars being given a field goal as they play host to the 5-3 San Francisco 49ers.
While the 49ers may be considered the superior team, their recent performance does not reflect that. Coming off a bye week, they have lost three consecutive games after starting the season 5-0, scoring only 17 points in each loss. Additionally, they have a 1-3 against the spread record on the road, suffering defeats to the Cleveland Browns and Minnesota Vikings.
The benefit of San Francisco having a bye week is canceled out by the fact that the Jaguars are also coming off a bye week. Prior to their break, Jacksonville had achieved five consecutive victories, including four by a significant margin, despite facing a challenging schedule that involved playing games overseas, returning home, and participating in a Thursday Night Football matchup shortly after.
In recent years, the Jaguars have proven to be a formidable home underdog by winning six of their last seven games in that position. Additionally, Jacksonville’s defense has had success against San Francisco’s potent running game, limiting opponents to less than 80 rushing yards per game this season.
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Denver Broncos are the underdogs with odds of +320 against the Buffalo Bills.
Many believed the Denver Broncos were finished after their embarrassing 70-20 loss to the Miami Dolphins in late September, but that assumption may have been premature. The team, led by Sean Payton, has won three out of their last five games, largely due to a defense that is starting to look like the elite unit from last year. In their last three games, Denver has only allowed a total of 45 points, including a surprising 24-9 victory over the Kansas City Chiefs. The Broncos are proving their resilience and potential for success as they head into the rest of the season.
Despite Denver’s surprising success, the Buffalo Bills have been disappointing. Their recent 24-18 loss to the Cincinnati Bengals marked their third defeat in the last five games. The Bills have only managed to secure victories against the New York Giants and Tampa Bay Buccaneers, with a combined point differential of 11. Quarterback Josh Allen has thrown nine interceptions this season, and the offense has struggled to score, averaging just 20.2 points per game since early October.
It may be difficult to picture the Bills losing a crucial night game at home to Denver, but it was also unexpected to see Buffalo relying on late defensive stops to narrowly avoid defeat against the Giants and Bucs in other recent primetime matchups. With the contrasting trajectories of these two teams, I am willing to take a chance on the well-rested Broncos at this generous price.
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NFL upset predictions were made on 11/8/2026 at 2:25 p.m. ET.
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