The San Francisco 49ers have looked pretty freaking dominant through the first two weeks of the 2023 NFL season. Will they remain perfect by picking up a Week 3 victory over the New York Giants, who they face off against on Thursday, September 21, at 8:15 p.m. eastern standard time, on the field at Levi's Stadium in Santa Clara, California?
The best online NFL betting sites sure seem to think so. Here are the latest San Francisco 49ers vs. New York Giants betting odds:
Favorite 
Underdog San Francisco 49ers -590 +430 New York Giants
Always remember to double-check these NFL online betting odds until you actually submit your wager. Our Giants vs. 49ers odds are accurate entering Tuesday, September 19. The best betting sites for the 2023 NFL season will keep making line adjustments right up until opening kickoff.
This game, in particular, is one in which we would expect for there to be real line movement. Though the Niners are already opening as heavy favorites, the Giants are dealing with an injury to star running back Saquon Barkley. Public sentiment could change depending on his status or whether New York signs another halfback off the free-agent market. Barkley is currently week-to-week with a sprained ankle, so he may not be ruled out or cleared to play until the 11th hour.
Granted, Barkley’s status won’t do anything to overhaul the current Niners vs. Giants betting odds. San Francisco has moved to the top of the pecking order for early betting on the Super Bowl. And that’s not an accident. They have looked incredible on both sides of the ball so far. Will that continue in Week 3? Let’s get to our Niners vs. Giants picks!
Do the New York Giants Even Have a Realistic Path to Upsetting the San Francisco 49ers?
There’s really no need to spend much time on the Niners’ case to beat the Giants. Everything about them screams “Potential Super Bowl Favorite.” They juuust beat the division rival Los Angeles Rams in a rollicking 30-23 victory. San Francisco has now notched 30 points in each of their first two games, on the back of an offense that looks absolutely dangerous. Quarterback Brock Purdy has yet to eclipse 300 passing yards in a single contest, but he has, for the most part, done a nice job of stewarding the offense.
Superstar running back Christian McCaffrey, meanwhile, looks like a potential MVP candidate. He’s cleared the 115-yard rushing plateau in both of the Niners’ games, on top of everything he adds to the passing game, as both an actual and conceptual threat defenses don’t know how to handle.
Perhaps optimists can talk themselves into the Giants putting up a fair fight. Quarterback Daniel Jones just put up 321 passing yards against the Arizona Cardinals in New York’s come-from-behind Week 2 victory. And he connected on a big play with wideout Jalin Hyatt, suggesting the Giants might be ready to let him work in more downfield throws.
Then again, all the metrics point to New York’s offense remaining wildly mediocre, if not much worse. Let’s not pretend they won't desperately miss Barkley, either. We would be shocked if he played against San Francisco. The Giants are working on a short week, and they need him to be healthier for the longer haul.
To New York’s credit, they do sport a pretty decent defense. They might be able to limit a somewhat conservative San Francisco passing attack. At the same time, the Giants rank 26th in net yards allowed per passing attempt and are currently 25th in interceptions. They’re not exactly dominant. Complicated still, New York’s run defense hasn’t been up to snuff. Only one team has allowed more rushing touchdowns, and the Giants are also 24th in net yards allowed per rushing attempt.
In the end, this feels like a game New York can’t win. And that’s why, without hesitation, we’re rolling with the home team.
OSB Prediction: San Francisco 49ers (-590)
The Point Spread for New York vs. San Francisco is Mighty Interesting
Linemakers are currently predicting a blowout for this head-to-head. You can see the latest point spread betting odds for Giants vs. 49ers just below:
- San Francisco 49ers, -10.5 (-115)
- New York Giants, +10.5 (-105)
Investing in the Giants looks a little tempting. The Niners could take their foot off the gas if they open up a big lead.
Still, New York struggled to move the ball in the first half against Arizona’s defense. Imagine trying to break through the Niners’ defense with an underwhelming air game and without your superstar running back.
Predicting blowouts always makes us a little uneasy—especially this early in the season. The NFL remains an anything-can-happen league. In this matchup specifically, though, we’d be surprised if the Niners win by fewer than two touchdowns.
How much will the Giants Score Against the 49ers Defense?
Apparently linemakers have some level of faith in New York’s offense figuring out ways to score. That’s our takeaway from the latest NFL over/under betting odds on 49ers vs. Giants:
- Over 44.5 (-110)
- Under 44.5 (-110)
To be honest, this feels a little ambitious. The number seems to be inflated because the Giants just topped 30 points without getting a score from Barkley. But the Niners defense has allowed just 30 combined points through two games. And without a strong running game or offensive line to go up against, they should absolutely feast in this one.
Of course, things get interesting if you pencil in San Francisco for 30 points of their own. But you have to ask: Can you really trust the Giants to score more than two touchdowns? Maybe you do. We do not.
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