Broncos vs. 49ers Score Prediction for NFL Week 4 (How to Bet on Sunday’s Marquee Matchup)

A marquee matchup is set for Week 4’s late window, as the Denver Broncos hit the road for their second straight matchup with an NFC West foe, this time taking on the San Francisco 49ers.

San Francisco has knocked off the Los Angeles Rams, Miami Dolphins and Arizona Cardinals to start the season 3-0, and they’re favored at home against a Denver team that just upset the Rams on Sunday night.

The Broncos have won two games in a row after losing badly to Kansas City in Week 1, but they have a tough test against Brock Purdy (No. 2 in the MVP voting) and this elite San Francisco offense (No. 1 in EPA/Play). The Broncos have struggled a bit against the run, yet their defense is No. 9 in EPA/Pass despite facing Patrick Mahomes, Trevor Lawrence and Matthew Stafford the first three weeks of the season.

Bo Nix has been the come-from-behind king, and he and the Broncos would love to pick up another upset win to move to 3-1. Can they make it happen in San Francisco?

All season long, the SI Betting is sharing final score predictions to help bettors lock down their moneyline, spread and total bets. Plus, we may end up hitting an exact score along the way!

This could be a Super Bowl matchup in February, so let’s dive right into the final score prediction for the regular season clash between these two contenders.

Broncos vs. 49ers Odds, Spread and Total

Odds via DraftKings Sportsbook

Spread

Broncos +3 (-120)
49ers -3 (+100)

Moneyline

Broncos: +124
49ers: -148

Total

47.5 (Over -110/Under -110)

There has been a little line movement in this game since it opened with the 49ers as 3-point favorites. San Francisco remains in that spot, but the odds (-120 on Denver +3) have shifted slightly towards the Broncos after their win against the Los Angeles Rams in Week 3. Plus, the total has jumped from 45.5 to 47.5 – a notable swing – since Sunday night.

Broncos vs. 49ers Score Prediction

SI Betting’s Iain MacMillan shares his favorite bet for every game, every week in his Road to 272 column, and he’s taking the 49ers to cover:

By a lot of metrics, the San Francisco 49ers are the best team in the NFL through the first three weeks. They are first in Net Yards per Play (+2.5), first in EPA per play, and first in success rate. To be fair, two of their first three games came against the Dolphins and Cardinals, but I'm extremely high on this team.

Now they get to face a Broncos team that I'm still not sold on. They managed to win two games at home, a historically tough place for opponents to play in September, and the game against the Rams finished with a handful of questionable calls that went Denver's way. Overall, the Broncos are 25th in Net Yards per Play (-0.6), and Bo Nix is just 26th in adjusted EPA per play and 27th in completion percentage over expected.

With the spread below a field goal, I think the 49ers are a great bet on their home field.

MacMillan and I actually happen to be on opposite sides in this game, but I do think the 49ers will win – even if they don’t cover.

I’m worried about this San Francisco defense without Bosa (and potentially Dre Greenlaw) against a Denver team that is a lot better than Miami and Arizona. The 49ers are just 19th in success rate and 15th in EPA/Play this season, a shaky ranking since they’ve faced two of the worst teams in the NFL.

Meanwhile, Denver is 10th in EPA/Pass despite facing three quarterbacks in the MVP conversation. The Bronco offense hasn’t been anywhere near as good as the 49ers, but is San Francisco’s offense being propped up by favorable matchups?

The Broncos have shown they aren’t going to roll over even if they fall behind, and Arizona was able to orchestrate a backdoor cover against the 49ers in Week 3. If San Francisco struggles to get stops, I could see this game coming down to the final possession.

Final Score Prediction: 49ers 27, Broncos 26

Odds refresh periodically and are subject to change.

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