NFL Odds Week 3: Giants vs 49ers Lines, Spreads, Betting Trends

Matchup Spread Total Moneyline

As Week 3 of the NFL season approaches, the betting odds come into focus, and the action kicks off in the Bay Area on Thursday night. The Giants and 49ers are set to ignite the excitement at Levi's Stadium in Santa Clara on Thursday, September 21, with the game scheduled for 8:15 p.m. ET and exclusive coverage available on Amazon Prime.

Here's everything you need to know about the NFL odds for the Week 3 game between the Giants and 49ers: the opening lines, spreads, betting trends and more. Check back regularly for updates.

New York Giants vs San Francisco 49ers Odds

The 49ers seek a perfect 3-0 start when they host the Giants on Thursday. (Getty)
  • Opening point spread: 49ers -9.5
  • Opening moneyline: 49ers -600/Giants +425
  • Opening total: Over/Under 45.5 points scored
  • Time: 8:15 p.m. ET Thursday (Prime)

UPDATE 3 P.M. ET THURSDAY: A few hours ahead of kickoff, San Francisco is a 10.5-point favorite at PointsBet, a Fanatics Experience. That's up a half-point from Sunday's Niners -10 opener, with San Fran peaking at -11 Monday and since then toggling between -10.5 and -10.

Bettors aren't shying away from the double-digit spread. Ticket count is 2.5/1 and money almost 5/1 on the 49ers. But the moneyline of 49ers -575/Giants +420 is going the other way, no surprise.

"Although the Giants are without Saquon Barkley and two starting offensive linemen, we have a significant liability on the Giants moneyline," PointsBet sports trader Will Radice said. "Bettors are hoping for the Giants to continue the offensive momentum in the second half of last week's comeback vs. the Cardinals."

PointsBet opened the total at 45 and briefly touched 46 Monday. But it's been sliding back since then, bottoming out at 43.5 this morning. That said, tickets and money are in the 2/1 range on the Over.

On the player props front, PointsBet has 49ers running back Christian McCaffrey -250 in the anytime touchdown market. That's the steepest price for any NFL player this season, but it's still PointsBet's most popular prop tonight, taking the most tickets and money.

Perhaps as interesting, San Francisco's defense/special teams has shorter odds to score a TD tonight, at +425, than any New York receiver.

UPDATE 5 P.M. ET WEDNESDAY: The Giants won't have running back Saquon Barkley (ankle) for the first game on the NFL Week 2 odds docket. But that was already baked into the cake at TwinSpires Sportsbook, where the 49ers opened and remained -10.

San Francisco is taking 60% of early spread tickets/62% of early spread money.

"We're expecting San Francisco moneyline parlays and teasers to be popular again this week," TwinSpires director of retail trading Zachary Lucas said.

TwinSpires' total opened at 43.5 and is up to 44.5. The Over is seeing 57% of tickets/63% of money.

UPDATE 9:30 P.M. ET SUNDAY: New York notched a fortuitous Week 2 victory, but also suffered a potentially significant loss. The Giants looked awful in the first half against the Arizona Cardinals, trailing 20-0 to stretch their 2023-24 scoreless streak to six quarters.

Then the G-Men rallied in the second half, winning 31-28 on a last-minute 34-yard field goal. New York (1-1 SU/0-2 ATS) failed to cover as a 4.5-point road favorite.

Late in the fourth quarter, Giants running back Saquon Barkley suffered an ankle injury. With a short turnaround this week, that's one to keep an eye on, and it could be a longer-term issue.

Meanwhile, San Francisco (2-0 SU/1-1 ATS) beat the Los Angeles Rams 30-23. But L.A. made an otherwise meaningless field goal as time expired, so the Niners failed to cover as 7.5-point faves.

San Fran is already up to double digits in The SuperBook's NFL odds Week 3 market.

"We took a sharp bet on the 49ers -9.5 shortly after opening, moving us up to -10," SuperBook risk supervisor Casey Degnon said tonight. "I expect the public to be on the Niners via teasers and moneyline parlays. But I could see the straight-bet ticket count being somewhat close.

"That may have been a different story if the Giants didn't come back from 20 down at the half."

The total is stable at 45.5.

"Nothing to the total yet, but I wouldn't be surprised if there is some rare public love for the Under here," Degnon said.

Click here for Vegas Insider senior reporter Patrick Everson's full NFL Odds Week 3 Report containing spreads, lines, and trends for every NFL matchup.

The One Stat to Know About Giants vs 49ers

Action Network NFL researcher Evan Abrams offers his top betting stat:

Daniel Jones has played 12 games on short rest with the Giants and he's 4-8 SU, but 9-3 ATS – 9-1 ATS on short rest since 2020. Since his first start in 2019, Jones is most profitable QB ATS on short rest.

For more NFL Week 3 picks, check out Action Network's NFL Week 3 Betting Trends, Stats, Notes.

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