49ers vs Giants Odds, Picks, Player Props: Thursday Night Football Best Bets

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49ers vs Giants Odds

Thursday, Sept. 21
8:15 p.m. ET
Prime Video
49ers Odds
SpreadTotalMoneyline
-10.5
-105
43
-110o / -110u
-600
Giants Odds
SpreadTotalMoneyline
+10.5
-115
43
-110o / -110u
+450
Odds via bet365. Get up-to-the-minute NFL odds here.

We start Week 3 with 49ers vs. Giants picks with San Francisco favored by 10.5 points as of 6:30 p.m. ET. Our staff has a pick on the spread and three player props to bet, and all of those are on the San Francisco side.

Check out our favorite 49ers vs. Giants picks and player props below.


49ers vs Giants Picks

The team logos in the table below represent each of the matchups that our NFL betting staff is targeting from today's slate of games. Click on the team logos for any of the matchups below to navigate to a specific bet discussed in this article.

GameTime (ET)Pick
8:15 p.m.
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Specific betting recommendations come from the sportsbook offering preferred odds as of writing. Always shop for the best price using our NFL Odds page, which automatically surfaces the best lines for every game.
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49ers vs. Giants

Thursday, Sept 21
8:15 p.m. ET
Prime Video
49ers -10.5

By Brandon Anderson

Thursday night smells like Blowout City.

The last three times the Giants played a top-tier team, it was ugly. They lost 40–0 to the Cowboys in Week 1 and lost by 31 and 26 in their last two games against the Eagles last season. Heck, this team needed a miracle second-half comeback last week just to beat the lowly Cardinals!

Head coach Brian Daboll helped raised New York's floor, but the ceiling still isn't there. It's telling that the Giants had no discernible talent advantage against the least-talented roster in the NFL in Arizona.

San Francisco is vastly better and tends to blow out opponents. The 49ers have won 12 straight regular-season games, and eight of those wins (67%) came by at least 13 points. The Giants were last in run DVOA defensively last year, so it smells like one of those games where the Niners get up early and then just chew up clock on the ground.

On top of the talent deficit, New York is missing three of its best players in RB Saquon Barkley, OT Andrew Thomas and LB Azeez Ojulari due to injury. The offensive line, in particular, is an absolute disaster for this team right now and has no shot against Nick Bosa and the Niners defense.

I don't make a habit of playing double-digit favorites, but Thursday favorites of seven or more points are 40–26 (61%) against the spread (ATS), while Thursday ‘dogs that just won by three or fewer the previous week – like the Giants – are 11–18 ATS (38%).

I grabbed San Francisco -10 on the Hot Read and still think this line rises by kickoff. I like the Niners anywhere under -13.

Pick: 49ers -10.5


Bet San Francisco vs. New York at FanDuel

49ers -10.5

Giants +10.5



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49ers vs. Giants

Thursday, Sept 21
8:15 p.m. ET
Prime Video
Brock Purdy Under 7.5 Rushing Yards

By Grant Neiffer

This line is way off with the game script being a positive one for the 49ers.

Purdy has been taking off early on this season with six rushing attempts, but he's not a good running quarterback.

The game spread is sitting at 10 right now and the Giants have looked terrible outside of one half last week, so I won't be surprised if this game is a blowout.

Purdy is mostly going to run the ball in close games, which I don't see as an outcome in this game. He has hit the over only once in 11 career games, and he only has 38 career rushing yards.

Quarterbacks have only run four times in two games against the Giants this season. I wouldn't be surprised to see Purdy not have a single rushing attempt.

I'd hit this line all the way down to 5.5 yards.

Pick: Brock Purdy Under 7.5 Rushing Yards


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49ers vs. Giants

Thursday, Sept 21
8:15 p.m. ET
Prime Video
Nick Bosa Over 0.75 Sacks (-105)

By Cody Goggin

Daniel Jones and the Giants may be in for a rough night on Thursday. With injuries to Andrew Thomas and Ben Bredeson, the New York offensive line is already going to be shaky. The injury to Saquon Barkley is going to further compound the effect that this has on Daniel Jones, who will be relied on to throw the ball more.

While pressures and sacks can happen because of your OL, they also are a quarterback stat. Last year Daniel Jones took 51 sacks, which was tied for the third-highest mark in the league. According to Pro Football Focus, Daniel Jones had the fifth-most allowed pressures among QBs last season. While Jones can be a playmaker with his legs, he does tend to hold onto the ball sometimes for longer than he should, resulting in these higher pressure rates.

The offensive line has not done Jones any favors this year either. Currently Jones has been pressured the second-most times in the league. He has already been pressured 41 times and taken 10 sacks in two games.

Most of this pressure on Jones has come from the right side of the line, as 35.3% can be attributed to the right guard and 26.5% to the right tackle position. That right tackle would be Evan Neal, who is tied for the third-most pressures allowed in the league this season.

At right guard in week one was Mark Glowinski, who allowed nine pressures and three sacks against the Cowboys, putting up a PFF pass blocking grade of 1.0. Yes, you read that right. He did better after moving to left guard against the Cardinals, but his replacement, Marcus McKethan, also struggled with three pressures allowed and a PFF pass blocking grade of 54.1.

The 49ers like to move their defenders around, as Nick Bosa primarily played as the left end last week after playing on the right in week one. I would look for the Niners defense to already have these mismatches schemed up.

Nick Bosa has nine pressures this season, but they have not resulted in any sacks yet. I look for this regression to finally hit and Bosa to get at least a full sack on Thursday night. I’d take this up to -115.

Pick: Nick Bosa Over 0.75 Sacks (-105)


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49ers vs. Giants

Thursday, Sept 21
8:15 p.m. ET
Prime Video
Christian McCaffrey Under 17.5 Rush Attempts

By Ricky Henne

The 49ers have relied almost exclusively on Christian McCaffrey at running back thus far, and can you really blame them? He’s arguably the NFL’s most dangerous weapon.

However, they’ve gone overboard so far since he’s been on the field for all but 10 offensive snaps to start the season. McCaffrey played every single down last week against the Rams, and it would be borderline criminal to pound it out with him to the same extent on only three days' rest.

Head coach Kyle Shanahan appears to agree, telling the media he regrets how little Elijah Mitchell’s played thus far. He also said that continuing to use McCaffrey as much as the 49ers have is simply unsustainable.

McCaffrey carried the ball 20 times against Los Angeles in Week 2 and 22 times against Pittsburgh in Week 1. Even a small handful of Mitchell carries would easily cut into that number, which is why I’m a fan of the under on 17.5 carries.

The 49ers are also facing a hobbled Giants team that they should easily handle. Add it all up, and I’m hard-pressed to find a better scenario for the 49ers to ease McCaffrey’s workload and get Mitchell more involved.

Pick: Christian McCaffrey Under 17.5 Rush Attempts (-136)
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