Giants vs. 49ers odds, line, spread: Thursday Night Football picks, NFL predictions by model on 164-117 roll

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The San Francisco 49ers will try to get off to a rare 3-0 start  when they play their home opener against the New York Giants on Thursday Night Football. San Francisco (2-0), which has won 12 consecutive regular-season games, has begun a campaign with three straight victories just once in the last 25 seasons. The Giants (1-1) suffered an embarrassing 40-0 home loss to Dallas in their season-opener and trailed 20-0 at halftime in Arizona last week before matching a franchise-record by rallying from a 21-point and posting a 31-28 victory. New York could be without Saquon Barkley, however, after the star running back sprained his ankle against the Cardinals.

Kickoff from Levi’s Stadium is set for 8:15 p.m. ET. San Francisco is a 10-point favorite in the latest Giants vs. 49ers odds, while the over/under for total points scored is 44.5. Before making any 49ers vs. Giants picks, you need to see the NFL predictions and betting advice from SportsLine’s Advanced Computer Model.

The model, which simulates every NFL game 10,000 times, is up more than $7,000 for $100 players on top-rated NFL picks since its inception. The model enters Week 3 of the 2023 NFL season on an incredible 164-117 run on top-rated NFL picks that dates back to the 2017 season. It is also on an 18-9 roll on top-rated NFL picks since Week 7 of last season.

The model also ranked in the top 10 on NFLPickWatch four of the past six years on straight-up NFL picks and beat more than 94% of CBS Sports Football Pick’em players four times during that span. Anyone who has followed it is way up.

Now, the model has set its sights on 49ers vs. Giants and just locked in its picks and Thursday Night Football predictions. You can head to SportsLine now to see the model’s picks. Here are several NFL odds and betting lines for Giants vs. 49ers: 

  • Giants vs. 49ers spread: San Francisco -10
  • Giants vs. 49ers over/under: 44.5 points 
  • Giants vs. 49ers money line: San Francisco -547, New York +401
  • SF: 49ers are 14-8 against the spread, including playoffs, since the start of the 2022 season 
  • NYG: Giants are 0-2 ATS this year after going 14-5 in 2022, including playoffs
  • Giants vs. 49ers picks: See picks at SportsLine

Why the 49ers can cover

San Francisco could be missing a top offensive weapon on Thursday Night Football, as wide receiver Brandon Aiyuk suffered a shoulder injury in the team’s 30-23 victory against the Los Angeles Rams in Week 2. The 25-year-old played through it, but finished with only three receptions for 43 yards. If Aiyuk is unable to go, second-year quarterback Brock Purdy still has plenty of options to target, with Deebo Samuel topping the list.

Samuel hauled in six passes for 63 yards against the Rams and also ran for an 11-yard touchdown in the fourth quarter. A limited or absent Aiyuk also could mean more action for George Kittle, who tied for third in the NFL last season with a career-high 11 TD catches. The 29-year-old Kittle was fifth among tight ends in 2022 with 765 yards on 60 receptions despite missing two contests. See which team to pick here.

Why the Giants can cover

New York was outscored 60-0 over its first six quarters of the season and fell behind 28-7 late in the third quarter against Arizona before coming alive. The Giants scored 24 unanswered points to match the largest comeback in franchise history, most recently accomplished in 1949 versus the Chicago Cardinals. Quarterback Daniel Jones completed 81% of his attempts in the second half and finished with 321 passing yards and two touchdowns while also running for 59 yards and a score.

The 26-year-old became the first player in Giants history to register 250 passing yards, 50 rushing yards, two TD passes and a rushing score in the same game, all of which he recorded in the second half. He was 26-of-37 in the victory and may have found a No. 1 target in wide receiver Jalin Hyatt. A third-round pick in this year’s NFL Draft, the 21-year-old rookie’s first career reception went for 58 yards on the first play of the second half, and he had a 31-yard catch in the fourth quarter that led to New York’s game-tying touchdown. See which team to pick here.

How to make 49ers vs. Giants picks on TNF

SportsLine’s model is leaning Over the point total, calling for 46 combined points. The model also says one side of the spread cashes in nearly 60% of simulations. You can only see the model’s TNF picks at SportsLine.

So who wins 49ers vs. Giants on Thursday Night Football, and which side of the spread cashes almost 60% of the time? Visit SportsLine now to see which side of the 49ers vs. Giants spread you need to jump on, all from the model on a 164-117 roll on NFL picks, and find out.

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