49ers vs. Broncos Point Spread: NFL Week 3 Odds, Prediction

Payton Matthews | Updated Sep 23, 2022

It’s another prime-time game for new Broncos quarterback Russell Wilson already early this season as Denver hosts San Francisco in the Sunday night matchup in Week 3.

September 25, 2022, 8:20 PM ET
Empower Field at Mile High
Pointspread -1 -112
Moneyline -123
Over / Under o +44.5


Betting Action


Pointspread +1 -108
Moneyline +102
Over / Under u +44.5


Betting Action


The Niners are 1.5-point favourites on the NFL odds.

NFL Week 3 Point Spread and Betting Analysis

It’s not impossible that 49ers-Broncos is a potential Super Bowl 57 preview, but I won’t be wagering on that exacta at the moment. New Denver quarterback Russell Wilson is very familiar with San Francisco from his NFC West days with Seattle. Wilson is 16-4 in his career against the Niners, completing 64.7 percent of his passes for 36 touchdowns and 10 picks. This was to be the first prime-time start for second-year 49ers quarterback Trey Lance, but that will no longer be the case.

It’s the first meeting between these teams since December 2018 when the 49ers won 20-14 at home. The quarterbacks that day: Case Keenum and Nick Mullens. Both are long gone.

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San Francisco 49ers

Ahead of the 2021 NFL Draft, the Niners sent their ’21, ’22 and ’23 first-round picks and a 2022 third-rounder to Miami to move up to No. 3 overall and select North Dakota State quarterback Trey Lance. Smart or terrible move? We won’t have that answer until 2023 at the earliest as Lance broke his ankle in Sunday’s 27-7 win over Seattle and will miss the season – meaning he will have started a total of four games his first two years. A lot of people around the NFL think the Niners are better right now with Jimmy Garoppolo regardless, and it’s his team again. He hasn’t exactly proven durable himself, though, and the only other QB on the roster as of this writing was the final pick of the 2022 draft, “Mr. Irrelevant” Brock Purdy.

Pro Bowl tight end George Kittle hasn’t played yet this season due to injury but might Sunday. That would be helpful as the No. 2, Tyler Kroft, was hurt in Week 2 and will miss a while. Rookie running back Tyron Davis-Price also will miss a few weeks; he became a part of the rotation on Sunday with No. 1 Elijah Mitchell out a few months. The Niners are 4-1 ATS in their past five road games.

Denver Broncos

This will be Denver’s first prime-time home game where a full crowd is allowed (i.e., not including 2020) since a Week 7 matchup with the Chiefs in 2019. The Broncos have been wildly disappointing on offence so far despite the big offseason trade for future Hall of Fame QB Russell Wilson, and first-year coach Nathaniel Hackett is taking most of the blame due to consistent troubles with the play clock and penalties.

The Broncos have been assessed four delay of game penalties already. Hackett said he intends to keep play-calling duties. Two key Broncos were injured in Sunday’s ugly win over Houston: receiver Jerry Jeudy and stellar young cornerback Patrick Surtain II. Both are being called day-to-day. Denver is 1-5 ATS in its past six games, but we’ll lean it at home – the under 45 is probably the best bet.

NFL Prediction: Who Will Win 49ers vs. Broncos?