49ers vs Broncos Sunday Night Football Picks and Predictions: Matchup Favors Aiyuk

San Francisco and Denver are both coming off their first wins of the season in Week 2 and now clash on Sunday Night Football in the Mile High City. Find out our favorite edge in our 49ers vs. Broncos betting picks.

Last Updated: Sep 25, 2022 4:58 PM ET Read Time: 4 min
Brandon Aiyuk San Francisco 49ers
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It was already tough to breathe in the thin Rocky Mountain air without suffering a panic attack over your underperforming $245-million investment. But anxiety levels are "Mile High" for a Week 3 Sunday Night Football showdown between the so-far unimpressive Denver Broncos and the San Francisco 49ers.

Russell Wilson — the man behind those millions — and the Broncos have fallen short of expectations in the opening two weeks of play. The offense has mustered a total of just 32 points, and new head coach Nathanial Hackett looks like he’d have a tough time following the recipe for "Shake 'N Bake," let alone running a professional football team.

Stock is down on Denver, which has forced a notable line move for this non-conference clash — a move that might not be warranted if you dig a little deeper.

We do just that, sizing up the spread and total for Sunday Night Football and giving our best NFL picks and predictions for 49ers vs. Broncos on September 25.

You can also check out our 49ers vs. Broncos SNF prop picks for even more great bets!

49ers vs Broncos best odds

49ers vs Broncos picks and predictions

I did grab the points with the Broncos after the line move in my weekly NFL Underdogs column, but my focus here shifts to San Francisco and the change at quarterback for Kyle Shanahan’s playbook. 

Trey Lance is out for the season, which means defaulting back to Jimmy Garoppolo under center. Losing Lance definitely takes the danger element out of this offense, but the veteran is a bump in pure passing prowess — even if he’s making carefully calculated throws. 

Lance wasn’t exactly letting it rip in his first two games, averaging just 6.7 intended air yards per attempt. Jimmy G upped that metric to 8.3 when he stepped in versus Seattle last week. Granted, some of those passing stats have been tempered by two bad weather games for the 49ers, but Garoppolo gives a higher ceiling to the San Fran receivers in Week 3.

One guy who will thrive with Jimmy G back in the mix is WR Brandon Aiyuk, who emerged as one of Garoppolo’s favorite targets midway through 2021. Aiyuk wrapped last year with 50 or more yards receiving in six of his final eight regular season games, as well as in two of three postseason matchups. 

Through two weeks of 2022 action, Aiyuk has seven catches on 11 targets for 103 total yards, with the bulk of those (63) coming against the Seahawks with Garoppolo under center. His latest Over/Under prop for receiving yards for Sunday Night Football stands at 49.5.

That's a very short uptick from his receiving yards totals in Week 1 (40.5) and Week 2 (45.5) when you consider his great chemistry with Garoppolo. Plus, there's the fact that the forecast is calm and clear for Denver after rain and wind slowed San Francisco down in the opening two games.  

On the other side of the ball, Denver’s defense definitely has not gotten enough credit, with the media aiming at new coach Nathaniel Hackett and the offense’s miscues. The Broncos' stop unit has been very stingy and comes into Week 3 ranked No. 6 in EPA allowed per play. 

That said, the Niners are the toughest offense Denver has faced in 2022, and this Broncos' depth chart is missing key parts of its pass defense as game day draws near. Star corner Patrick Surtain has been limited in practice this week, and safety Justin Simmons is still sidelined. 

Corner Ronald Darby will likely draw Deebo Samuel in coverage, which leaves Aiyuk to work against the shorter K’Waun Williams or rookie Damarri Mathis. With all of Shanahan's pre-snap motion causing mismatches, Aiyuk could also find himself covered by slower linebackers or safeties as the Broncos love to bring the blitz. 

Also working in Aiyuk’s favor in terms of receiving workload is a dinged-up 49ers rushing attack down its top two options, and TEs George Kittle (questionable) and Tyler Kroft (out) on the injury report.

My best bet: Aiyuk Over 49.5 receiving yards (-110 at bet365)

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49ers vs Broncos betting preview

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Spread analysis Over/Under analysis Trend to know Game info Injuries Weather

Spread analysis

The look-ahead line for this primetime game was set at Denver -2.5 in the spring. And even with the Broncos' loss at Seattle in Week 1 and a tight win over Houston at home in Week 2, books re-opened this spread at -2.5 last Sunday night.

The betting public doesn’t have a very positive opinion on Denver, with Hackett being blasted in the media and this Wilson-led offense unable to find the end zone. On top of that, San Francisco bounced back from a Week 1 loss at Chicago to roll over the Seahawks in Week 2 — the team that upset the Broncos in the opener. Those results had early action betting the Niners hand over fist in the first 48 hours of action.

Denver dropped quickly from -2.5 to +1.5 by Monday evening and has stayed at that spread most of the week. While the four-point adjustment is notable, it should be pointed out that this move didn’t go through traditional key numbers in football betting (3, 6, 7, 10) besides zero (always a debate on importance). According to the move in moneyline odds, the implied win probability shifted from Denver 54.55% to San Francisco 54.55%.

Injuries are stacking up for both teams. Denver could be without top WR Jerry Jeudy, who sat out practice Wednesday and Thursday, and standout corner Patrick Surtain was limited at practice.

Kyle Shanahan is down to a third-string RB, with TE George Kittle hoping to return. The big change for this playbook is losing Lance for the season and defaulting to Garoppolo, whom the team demoted to backup (and desperately tried to trade) this offseason.

As it stands Friday morning, the market consensus is San Francisco -1.5, with this spread ranging from -1 to -2 at select operators. Books like BetMGM are reporting 76% of bets and 78% of the handle on the visitor.

Over/Under analysis

This total has also seen movement. This Over/Under hit the board as low as 43.5 points on Sunday night and started ticking up with play on the Over. 

While the Broncos offense has struggled to score, going 0-for-6 inside the red zone in two games, this offense is still putting up big yards. Denver ranks out seventh in yards per play (6.1), No. 8 in EPA per play, and Over bettors are convinced Wilson & Co. will finally find paydirt in Week 3.

That optimism has boosted this number as high as 46 points, but injury concerns and buyback on the Under has since slimmed the total to as low as 44.5 points as of Friday. BetMGM is reporting interesting splits, with 63% of bets on the Under but 60% of money backing the Over Sunday night.

49ers vs Broncos betting trend to know

As a member of the Seahawks, Russell Wilson owned a 16-4 SU record in 20 career matchups with the 49ers. Wilson boasted a QB rating of 100.2 in those contests, with 36 touchdowns and 10 interceptions while picking up 7.31 yards per pass attempt. Find more NFL betting trends for 49ers vs. Broncos.

49ers vs Broncos game info

Location: Empower Field at Mile High, Denver, CO
Date: Sunday, September 25, 2022
Kickoff: 8:20 p.m. ET
TV: NBC

49ers vs Broncos key injuries

49ers vs Broncos weather

Monitor gametime conditions with our live NFL weather info and learn how weather impacts NFL betting.

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