This article is part of our NFL Picks series.
Giants vs. 49ers Betting Odds, Picks and Predictions for Thursday Night Football, Sept. 21
Thursday Night Football kicks off Week 3 with a matchup between the New York Giants and the San Francisco 49ers. After sifting through all of the wagering options, here are three bets that could prove to be profitable.
49ers vs. Giants Betting Odds for Thursday Night Football
49ers: Spread -10.5 (-108), -535 Moneyline
Giants: Spread +10.5 (-112), +410 Moneyline
Game Total: 44 points
Both teams are dealing with key injuries on a short week. The Giants will be without Saquon Barkley (ankle), while the 49ers are uncertain about the status of Brandon Aiyuk (shoulder).
49ers vs. Giants Betting Picks This Week
After getting shut out through their first six quarters of the season, it looked like the Giants were in big trouble. However, they came alive in the second half against the Cardinals in Week 2. Darren Waller played a key role in the comeback, coming up with several big catches down the stretch. He was targeted eight total times, which he turned into six receptions for 76 yards.
With Barkley having already been ruled out, the Giants are going to have to rely on their passing game if they are going to pull off the upset. They added depth at wide receiver during the offseason, but they still don't have any true number one option. With Waller being arguably the best target that Daniel Jones has, look for him to get plenty of opportunities to reach this over.
49ers vs. Giants Best Bet: Darren Waller over 45.5 receiving yards (-125 DraftKings Sportsbook) for 1 unit
Let's face it, Thursday Night Football games are sloppy. Teams are dealing with less rest, more injuries and fewer days to prepare. The 49ers have a lot of weapons on offense, so even if Aiyuk is out, they should be able to move the ball. They are also facing the same Giants defense that allowed Joshua Dobbs and the Cardinals to score 28 points.
With the 49ers being so proficient on offense, Jake Moody has received three field goal attempts in both of their games. He made all of them, including one from over 50 yards in Week 2. If the 49ers have a couple of drives stall out before getting into the end zone, look for Moody to convert on his opportunities and hit this over.
49ers vs. Giants Best Bet: Jake Moody over 1.5 field goals made (-115 DraftKings Sportsbook) for 1 unit
Barkley isn't the only notable injury for the Giants. They will also be without two starting offensive linemen, with Andrew Thomas (ankle) and Ben Bredeson (concussion) having been ruled out. That could end up being a disaster for Jones, who has already been sacked 10 times over two games.
Not only could the 49ers rack up sacks in bunches, but the Giants are still looking for their first sack of the season. Purdy has been sacked a modest four times over his first two games. The 49ers have a much better opportunity to record a sack before the Giants do.
49ers vs. Giants Best Bet: 49ers First Sack Recorded (-140 DraftKings Sportsbook) for 1 unit
49ers vs. Giants Prediction
It's difficult to envision a path for the Giants to win this game. Even if Barkley were healthy, they would be facing an uphill battle against a much better team. Add in the injuries to their already-struggling offensive line and the Giants are likely to have a hard time putting points on the board. Look for the 49ers to win this in convincing fashion.