San Francisco 49ers vs. Denver Broncos Picks, Predictions, Odds

Michael Crosson Sports Betting Expert

3 minute read

The fourth Sunday of regular-season NFL action will conclude with a compelling non-conference battle between the San Francisco 49ers and Denver Broncos. Coverage begins from Mile High Stadium in Denver at 8:20 p.m. ET on NBC.

Updated on 03/17/2026

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SAN FRANCISCO 49ERS vs. DENVER BRONCOS BETTING PREDICTION

The Niners stumbled out to a bumpy start with QB Trey Lance at the helm, as San Francisco scored just 10 points on 331 total yards in a wild slip-and-slide game against Chicago in Week 1 (L, 19-10). That was followed by another relatively slow start against Seattle in Week 2, as they scored 21-of-27 points following Jimmy Garoppolo’s entry on their final drive of the first quarter.

Denver, on the other hand, is also having an underwhelming start with a new signal-caller under center, considering the Broncos averaged just 16 PPG on 392 YPG in their first two contests following the blockbuster acquisition of Russell Wilson, which was still good for a 1-1 split against Seattle and Houston, but doesn’t bode well heading into much tougher matchups like Sunday night’s.

I’ll take the under here, as neither of these squads surrendered 20+ PTS in a matchup through the first two weeks of the season, with both defenses currently boasting an average of 13 points allowed per game; and while that trend might not quite continue this Sunday, I expect to see another low-scoring battle between these two struggling offenses.

Score Prediction: Broncos 23, Niners 17
Best Bet: Under 44.5 (-110)

SAN FRANCISCO 49ERS vs. DENVER BRONCOS BETTING BETTING ODDS

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SAN FRANCISCO 49ERS vs. DENVER BRONCOS BETTING BETTING RESOURCES

Date: Sunday, Sept. 25, 2022
Matchup: NFC West vs. AFC West
Venue: Mile High Stadium
Location: Denver, Colorado
Time-TV: NBC, 8:20 p.m. ET

SAN FRANCISCO 49ERS BETTING ANALYSIS

San Francisco wasn’t expected to do much in the postseason, especially after drawing Dallas in the first round, however, they certainly did some damage, as San Francisco posted stunning upset victories over the Cowboys and Packers en route to last year’s NFC Championship Game, where they came very to pulling off a three-game season sweep of L. A. but the Rams prevailed by a slim three-point margin (L, 20-17).

Despite their deep playoff run, the Niners decided to go in a different direction at quarterback to start this season, as San Francisco attempted to trade Garoppolo to pave the way for Trey Lance to take the reins, but they couldn’t find a suitor, so they’re stuck with him; but after last week’s unfortunate turn of events, I think it’s safe to say the Niners are glad he stuck around.

DENVER BRONCOS BETTING BETTING ANALYSIS

The Broncos saddled up for last year’s homestretch sitting well within striking distance of a playoff spot at 7-6. However, Teddy Bridgewater suffered a season-ending injury in Week 14 and Denver limped to the finish line with an 0-4 skid, which resulted in their relatively lackluster 7-10 mark for the season.

Denver’s defense is rarely the issue, as the Broncos ranked second in points allowed and ninth in total defense last season (18.9 PPG, 326 YPG), despite receiving very little support from their offense (19.7 PPG, 331 YPG). So, the addition of Wilson seemed like an easy fix, but time will tell how Denver’s roster actually stacks up regarding Super Bowl contention.

SAN FRANCISCO 49ERS vs. DENVER BRONCOS BETTING BETTING TRENDS

• The Niners are 6-1 ATS in their last seven games.
• The Broncos are 1-5 ATS in their last six games.
• The total has gone UNDER in five straight Niners' games.
• The total has gone UNDER in 10 of Denver's last 13 games.
• The Niners are 6-3 ATS in their last nine games against Denver.
• The total has gone UNDER in four of the last six matchups between the Niners and Broncos.
• The total has gone UNDER in six of San Francisco's last seven road games.
• The total has gone UNDER in five of Denver's last seven home games.
• The Broncos are 4-1 SU in their last five home games against San Francisco.

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Michael Crosson

Michael Crosson began his time at VegasInsider as a freelance NBA writer back in 2019 while he continued to study Psychology and Biology at James Madison University. Following his graduation in 2021, Michael joined the team full-time, and he's been with VI ever since. Michael still writes NBA, NFL, and MLB for VI, as well as gambling industry news. He's also become a crucial part of our editorial production team. More from Michael Crosson