If you’re sick of watching the New York Giants in prime time, I promise you that you’re not alone. The Giants have lost by a combined 79 points in their three national TV games this year and will be facing a Buffalo Bills team looking to get back on track after a disappointing loss in London to the Jacksonville Jaguars. But before we get into our Giants vs. Bills predictions, let’s preview this game.
Daniel Jones is out for this one with a neck injury, and Tyrod Taylor will be starting in his place for the Giants. This is a revenge game for both Taylor and head coach Brian Daboll, as they will each be going against their former team in Buffalo for the first time.
The Giants vs. Bills odds include the highest point spread of the week, which has only gone up since Jones was ruled out. For the Bills, this will be the 11th time with Allen at quarterback in which they have been favored by at least 13 points. According to Evan Abrams at The Action Network, the Bills are 9-1 SU and 5-3-2 ATS in those previous 10 games. So if you’re thinking of taking the Bills in your survivor pool, that should give you even more confidence.
With such a large point spread, how should you be betting on this game? Let’s check out the Giants vs. Bills predictions, picks against the spread, player prop bets, and more from the PFN betting team.
Our Betting Lines page has the freshest lines and promos to get BANG for your buck. PFN’s FREE Parlay Calculator and Betting Odds Calculator are also available for your betting process! New to sports betting? Check out our guide on How to Bet on the NFL. Visit our Sports Betting Legal Tracker on how to bet legally in the U.S.
New York Giants vs. Buffalo Bills Betting Lines, Start Time, and More
All odds are from DraftKings Sportsbook unless stated otherwise.
- Spread
Bills -15 - Moneyline
Giants +800, Bills -1350 - Over/Under
44 - Game Time
8:15 p.m. ET - Location
Highmark Stadium - How To Watch
NBC, Peacock
Bearman:Â I have admittedly watched way too much of the Giants in the last few weeks, and I know one thing: Their offense stinks, like, really stinks.
MORE: Week 6 NFL Bets and Expert Picks
No offensive TDs in the first half of the entire season, and this stat is almost hard to believe — take out the second half of the Arizona game, and the Giants have scored one offensive touchdown in 18 quarters of football. Yes, ONE!
Pick: Giants team total under 13.5 points (-105 at DraftKings)
Blewis:Â I liked the Bills giving 7.5 first-half points earlier this week, but that number has gone up a lot, so I’m actually going to go in a different direction that sort of contradicts that.
The Bills’ loss in London last week would be pretty insignificant in the grand scheme of things if they didn’t lose two of their best defensive players to injury in Matt Milano and DaQuan Jones. This was the second game in a row in which the Bills have lost key defensive players, as they put CB Tre’Davious White on IR the week prior.
If there’s any offense a banged-up defense would want to play against, it’s the Giant, who are incapable of blocking anyone and will be without Daniel Jones tonight. But giving 15.5 points is quite a lot and one that is very capable of losing on a backdoor cover when you consider the Bills’ injuries on defense.
MORE: Week 6 NFL Survivor Picks
What is giving me pause in taking the 15.5 with the Giants is the inability of their offense to keep pace with Josh Allen and Stefon Diggs early in this one. So I’ll probably live bet the Giants on the spread if/when they fall behind early and tease this with the Chargers in the Monday Night Football game. I mean, they gotta cover 21.5 points, right?!
Pick: Giants +21.5 and Chargers +7.5 in a six-point tease (-134 at FanDuel)
Soppe: I think we are getting a bit of a discount here after his eight-touch, 21-yard effort last week against the Jaguars (-4 rushing yards). He has at least 25 receiving yards in three of his past four games, a usage that can help bail us out if the ground game isn’t working — I just don’t think that’ll be the case.
For the season, the Giants miss the second-most tackles per game, and if Cook is going to be as involved as I project, that puts him in a great spot to break a big gain. Combine that with the fact that Cook sees a lightbox on 62.3% of his carries (10th-highest in the league), and we could be looking at a big performance.

Josh Allen is running less this season (4.0 carries per game, down from 7.8 last season), and it’s not crazy to think Buffalo could manage him in this spot: coming back from London with a road divisional game next week ahead of a Thursday nighter (vs. TB).
Cook has the same number of carries this season as Allen, Damien Harris, and Latavius Murray combined. He’s the lead back as a massive favorite; I’m happy to trust that role with my hard-earned dollar.
Pick: Cook to total 100 Scrimmage Yards (+180 at DraftKings)
Katz: Darren Waller’s groin injury appears to be more soreness than anything else, and it won’t keep him out tonight. That’s great. Now, it’s time to fade him.
Waller has had two strong outings against the Cardinals and Dolphins. In his other three games, he’s posted receiving lines of 3-36, 3-20, and 3-21.
The Bills are very stingy against the tight end. Just 14.3% of their total receiving yardage allowed has gone to the position. With Tyrod Taylor starting, I am not optimistic about Waller’s prospects this week.
Pick:Â Darren Waller under 39.5 receiving yards (-115 at DraftKings)

