Chiefs vs. 49ers Betting: Will Kansas City bounce back in the Bay Area against new-look Niners?

By | October 23, 2022

After throwing away a potential win in the final minutes for the second time this NFL season, Patrick Mahomes and the Kansas City Chiefs will look to get back on track on Sunday when they visit the San Francisco 49ers in a rematch of Super Bowl LIV.

This will be the first competitive matchup between Kansas City and San Francisco since they met with the Lombardi Trophy at stake on February 2, 2020.

That night at Hard Rock Stadium, the Chiefs memorably scored three late touchdowns to overcome a 20-10 deficit and claim their first Super Bowl title in 50 years.

Sunday’s showdown at Levi’s Stadium comes at a crucial time for both teams.

In last Sunday’s matchup of AFC title favorites, the Chiefs held a late lead against the Bills at home. But they gave up a late go-ahead touchdown, and Mahomes was picked off on the next drive to seal Kansas City’s 24-20 defeat.

The 49ers went into their Week 6 trip to Atlanta with back-to-back wins over the Rams and Panthers, but they had a rough game in a 28-14 loss against the Falcons.

Ahead of Week 7, Kansas City sits atop the AFC West, while San Francisco sits atop the NFC West.

So, things are certainly not all bad. But having three or four early losses is not ideal for having things remain that way, so Sunday’s matchup is very, very important for both teams.

Kansas City Chiefs vs. San Francisco 49ers Matchup Information and Betting Odds

Matchup Information

  • Matchup: Kansas City Chiefs (4-2, 2-1 away, 1st in the AFC West) vs. San Francisco 49ers (3-3, 2-0 home, 1st in the NFC West)
  • Venue & Location: Levi’s Stadium (Santa Clara, California)
  • Date: Sunday, October 23, 2022
  • Game Time: 4:25 p.m. Eastern Time (1:25 p.m. local time)
  • How to Watch Chiefs vs. 49ers: FOX

Chiefs vs. 49ers Early Odds

Game odds are via FanDuel. This article may also feature odds from our other recommended legal sports betting sites.


  • Kansas City Chiefs -3 (-110)
  • San Francisco 49ers +3 (-110)


  • Over 48.5 (-108)
  • Under 48.5 (-112)


  • San Francisco 49ers -164
  • Kansas City Chiefs +138

Chiefs vs. 49ers Gameday Odds

Game odds are via FanDuel as of Sunday, October 23 at 10:30 a.m. Eastern.


  • Kansas City Chiefs -1.5 (-108)
  • San Francisco 49ers +1.5 (-112)


  • Over 48.5 (-115)
  • Under 48.5 (-105)


  • Kansas City Chiefs -118
  • San Francisco 49ers +100

Kansas City Chiefs vs. San Francisco 49ers Prediction and Betting Picks

Chiefs vs. 49ers Prediction: Kansas City to win

Chiefs vs. 49ers Picks: Kansas City to cover (Best Value: -3 @ -108 at BetRivers) & Kansas City/San Francisco over (Best Value: over 48.5 @ -108 at FanDuel & BetRivers)

So, what do we make of these two teams? Both are still very much in the upper echelon of contenders, so there is still a lot of belief in what they bring to the table.

Currently, the Chiefs (+800) come in as the third favorite (second behind the Bills in the AFC) to win Super Bowl LVII, as per the latest odds at FanDuel.

The 49ers, meanwhile, are eighth in line (fourth among NFC teams, behind the Eagles, Bucs, and Vikings), coming in at +1900.

Current Super Bowl LVII Odds

  • Buffalo Bills +290
  • Philadelphia Eagles +550
  • Kansas City Chiefs +800
  • Tampa Bay Buccaneers +1100
  • Minnesota Vikings +1700
  • Los Angeles Chargers +1800
  • Baltimore Ravens +1800
  • San Francisco 49ers +1900

But if either one is to be one of the last two teams standing at State Farm Stadium in Glendale, Arizona on February 12 of next year, there are some things that will need to click in the big games.

As I mentioned in my Bills vs. Chiefs prediction, offensive balance has become increasingly important to Kansas City’s success.

And just like failing to achieve some form of balance and success on the ground in their Week 3 loss to the Colts, they didn’t against the Bills, tallying 68 yards on 18 carries (3.8 yards per carry).

And while it is rare for Mahomes to throw multiple interceptions in a game, the odds are against the Chiefs when he does. In his career, Kansas City is 4-7 in games in which Mahomes has thrown multiple picks.

One of those four wins was in Super Bowl LIV, when he threw two picks, including a fourth-quarter pick that seemingly all but sealed the win for the 49ers.

The Niners, who are starting a guy at quarterback that they actively tried to be done with, need balance even more to win.

But the Falcons never trailed, picked off Garoppolo twice, and held San Francisco well below its season average on the ground.

Rushing Numbers Entering Week 6 vs. Rushing Numbers in Week 6 for San Francisco 49ers

  • Entering Week 6: 4.6 yards per carry, 138.8 yards per game
  • In Week 6: 50 yards on 3.1 yards per carry

Jimmy G has gotten off of the mat a number of times, whether after injuries or underperformances or his team trying to replace him and trade him away. So, you definitely shouldn’t count out a big performance from him against Kansas City.

However, it’s not especially difficult–at least for me–to back the guy who is 62-18 as a starter in his NFL career and has lost back-to-back games only three times.

But if you need a little more convincing, here’s some worthwhile information to consider: On the four previous occasions Mahomes threw multiple picks in a Kansas City regular season loss, he led the Chiefs to a win in the next game each time.

Of those four wins, three were by double digits and three were on the road, and the Chiefs scored 45, 40, 42, and 31 points.

Does San Francisco’s Big Trade Change the Outlook?

This article was initially published prior to San Francisco’s blockbuster trade with the Carolina Panthers for former Stanford star Christian McCaffrey.

McCaffrey will be making his 49ers debut against the Chiefs, and the odds have certainly shifted.

But does this acquisition change my outlook about how this matchup will go? Not at all. I still favor Mahomes bouncing back from last week’s two picks and loss against Buffalo with a winning performance at Levi’s Stadium.

I was already on the over, which feels a lot more likely with the addition of one of the game’s most dynamic players.

It would be unreasonable to heap a lot of immediate expectations on McCaffrey, as you don’t know how he will be used in San Francisco’s offense. But he’s likely pretty happy to be out of a dysfunctional and disappointing situation with the Panthers.

More Chiefs vs. 49ers Content on Betting News

  • Chiefs vs. 49ers Consensus Picks, Score Projections & Betting Stats

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  • Bears vs. Patriots Prediction & Picks (Week 7 Monday Night Football)

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