New York Giants vs. San Francisco 49ers: Week 3 Predictions, Picks and Odds for Thursday Night Football 9/21/23

The San Francisco 49ers have ascended to Super Bowl favorites after two impressive victories to open the season.

They will look to make another statement in primetime when they host the New York Giants on Thursday Night Football.

New York needed a huge comeback to beat the woeful Arizona Cardinals in Week 2, so it’s not a surprise to see the 49ers listed as heavy betting favorites, per DraftKings on September 19.

Spread: 49ers -10
Moneyline: 49ers -550; Giants +410
Over/Under: 44.5 points

The 49ers are firing on all cylinders already and have a superior roster almost every place you look compared to the Giants.

San Francisco is at home and New York is on the second leg of two straight road games, which is even more reason to back the 49ers in this NFC matchup.

New York Giants vs. San Francisco 49ers Betting Prediction

The 49ers have the second-best point-differential in the NFL at plus-30 while the Giants sit at an NFL-worst minus-37. While it’s still early, those numbers are indicative of the talent level between these teams.

The Giants will be without star running back Saquon Barkley, which will make it even tougher sledding against an elite 49ers defense.

New York’s defense has struggled this year and will be hard-pressed to find an answer for the electric San Francisco playmakers, headlined by Christian McCaffrey, Deebo Samuel, Brandon Aiyuk and George Kittle.

The 49ers are huge moneyline favorites and I struggle to see a scenario in which this game is even close. Look for the San Francisco pass-rush to make life miserable on Daniel Jones and for the 49ers to cruise to the blowout win.

Prediction: 49ers 33, Giants 16

Prop Bet Prediction: San Francisco 49ers DE Nick Bosa Over 0.25 Sacks

Bosa doesn’t yet have a sack this season, but he’s still one of the best pass-rushers in the NFL.

Daniel Jones, meanwhile, has been sacked 10 times and has a propensity to hold the ball too long in the pocket.

The 49ers’ defensive front is menacing and Bosa leads the charge. The Giants will likely be in a position to throw the ball a lot because they could fall behind by double digits in the second half.

Bosa can pin his ears back and get after Jones. And not only would a full sack do the trick, but all he needs to do is combine for one in this matchup for the over to hit.

It’s the heavy favorite, but it’s still the right play.

How To Watch San Francisco 49ers vs. New York Giants

The San Francisco Giants will host the New York Giants on Thursday, September 21, 2023 at 8:15 p.m. ET at Levi’s Stadium in Santa Clara, California. The game can be seen on Amazon Prime Video.