NFL Computer Picks, Analysis and Best Bet For 49ers vs. Broncos on September 25, 2022

The Denver Broncos haven't looked great to start the season, but they can gain some momentum by knocking off the San Francisco 49ers in Denver on Sunday, September 25 at 8:20PM ET. Russell Wilson and the 49ers defense will be very familiar with one another from the star quarterback's time in Seattle. That should ultimately make this a fun chess match between the two teams. 

Find out how we think this one will play out in our 49ers vs. Broncos betting preview below. 

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49ers vs. Broncos Computer Picks

Predictive Analytics Data

• 56% chance the 49ers win on the money line
• 52% probability the 49ers cover the -1 spread
• 52% chance 49ers vs. Broncos goes Under 45 total points

For the best NFL computer picks, check out our 49ers vs. Broncos data predictions. They are constantly updating based on hundreds of different data points.

49ers vs. Broncos Analysis

The Spread

Trey Lance is a very talented football player, but his injury probably makes the 49ers a better football team today. Jimmy Garoppolo isn't anything special under center, but he knows how to run Kyle Shanahan's offense and Lance was going to need some more time to really get comfortable as the starter. 

Garoppolo isn't likely to light up many opposing defenses, but he'll be accurate with the football and get the ball in the hands of San Francisco's playmakers. With him in the mix, guys like Deebo Samuel and Brandon Aiyuk can do what they do best. The same goes for tight end George Kittle, who returns to the lineup after a groin injury kept him out two games. 

The problem for San Francisco is that the team is completely depleted at running back and defensive lineman Arik Armstead is out for this game. All in all, this team is just a little too beaten up to be counting on to win a road game on Sunday night.

MORE: NFL Futures Probabilities

We'd prefer to go with Denver in this football game. The Broncos have had some issues managing the clock early in the season, but that's something we expect them to figure out pretty shortly. This is still a talented football team on both sides of the ball, and Wilson generally plays his best football in primetime games. 

We haven't quite seen Denver explode offensively just yet, but that time is coming fast. The Broncos have a talented group of wide receivers, led by Courtland Sutton and his 11 catches for 194 yards. Sutton is Wilson's preferred target and should be one of the breakout stars of this season. We expect this passing game to get going a bit in this match-up, but it's the Broncos running game that should make the difference here. 

With San Francisco not at full strength along the line, it's tough for Shanahan to ask his group to completely shut down Javonte Williams and Melvin Gordon. That duo is one of the best the NFL has to offer in the backfield and it should play a big role in helping the Broncos keep this game tight and eventually steal it late. That's why we're on Denver +1. 

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The Over/Under

It's hard not to love the Under in a game like this, even when the total is a bit lower than you'd want it to be. These are two teams that like to run the football, and both have a lot of talent on the defensive side of the ball. With that said, the winner of this game might end up scoring no more than 24 or so points. 

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Since Shanahan became the head coach of the 49ers, the Under is actually 12-9 in games San Francisco has played in the first month of the season. We don't expect that to change here and it's also worth noting that the Under is 14-5 in all games the Broncos have played over the last two years. 

49ers vs. Broncos Best Bet

Under 45

We think the Under is the best bet in this game because both teams have run-first offenses, and San Francisco will double down on that approach now that Garoppolo is the quarterback again. These defenses should also be fired up with this being a night game on national television. 

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