The Detroit Lions (1-0) and the Buffalo Bills (1-0) meet Thursday for their Week 2 game in Orchard Park, New York, as the Bills open the brand-new $2.1 billion Highmark Stadium on Thursday Night Football. Kickoff is scheduled for 8:15 p.m. ET (Prime Video). Let's analyze NFL odds around the Lions vs. Bills odds and make our expert NFL picks and predictions for the best bets.
The Bills lead the all-time series 8-4-1, including a wild 48-42 win at Ford Field in Detroit on Dec. 15, 2024, in the most recent meeting. Buffalo has won 5 in a row in the series since 2006, the last win in the series for the Lions.
The Lions posted a 31-30 victory in overtime against the New Orleans Saints in Week 1, but it failed badly as a 7.5-point favorite as the Over
(49.5) cashed. QB Jared Goff threw for 206 yards and 2 TDs, both to WR Amon-Ra St. Brown, who finished with 10 grabs for 67 yards. RB Jahmyr Gibbs gobbled up 156 yards and 2 TDs, while adding 30 receiving yards, too.
The Bills outlasted the Houston Texans 36-31 as a 1.5-point road favorite as the Over (44.5) easily cashed. A 34-yard TD from QB Josh Allen to WR Joshua Palmer with 1:36 left in regulation put Buffalo ahead for good. Allen threw for 334 yards and 2 TDs, while running for 2 more scores. TE Dalton Kincaid had 5 receptions for 130 yards, and WR DJ Moore went for 5 receptions, 100 yards and a score.
Watch the NFL on Fubo!
Lions at Bills odds
Provided by BetMGM Sportsbook; access USA TODAY Sports Scores and Sports Betting Odds hub for a full list. Lines last updated Wednesday at 5:44 p.m. ET.
- Moneyline (ML): Lions +185 (bet $100 to win $185) | Bills -225 (bet $225 to win $100)
- Against the spread (ATS): Lions +5 (-108) | Bills -5 (-110)
- Over/Under (O/U): 54.5 (O: -112 | U: -105)
Lions at Bills injuries
Lions
- OL Christian Mahogany (hip) out
- OT Blake Miller (knee) out
- CB D.J. Reed (foot) questionable
Bills
- S Cole Bishop (knee, groin) questionable
- RB Ty Johnson (hamstring) questionable
- DL T.J. Sanders (knee, illness) questionable
USA TODAY Sports Fantasy: Sync your ESPN, Yahoo, CBS or Sleeper league in seconds to unlock custom roster advice, expert projections, and start/sit recommendations built for your team. Stop guessing and start winning. Sync your league now!
Lions at Bills picks and predictions
Prediction
Bills 31, Lions 27
Moneyline
The Bills (-225) will cost you more than 2 times your return, and that's way too much risk for not enough reward.
The truth is, both of these teams barely won last week, and it could go either way. Buffalo opens its new stadium, so the atmosphere should be electric. Of course, when isn't it electric on gameday in Western New York with the Bills Mafia?
PASS.
Against the spread
Back LIONS +5 (-108) lightly in this marquee matchup for Week 2.
Both teams showed off tremendous offense last week, but glaring defense on both sides means neither team should be out of it. A spread of 5 is quite high given when we saw last week from both teams.
Over/Under
OVER 54.5 (-112) is a rather high number. In fact, it's the highest number of the young season, as we had just 2 totals of an even 50 in the opening weekend. And, both of those games went Over, too.
Last season, Buffalo had a 9-8 edge to the Over, and Detroit was 10-7. Both teams are 1-0 this season, too. Let's go high, but we'll need a big start, and that's not always the case on a short week, so be cautious.
Betting odds calculator
For more sports betting picks and tips, check out SportsbookWire.com and BetFTW. Follow Daniel Dobish on X at @danieledobish. Follow SportsbookWire on X at SportsBookWire and on Facebook.
Access more NFL coverage:
USA TODAY Sports Fantasy | BearsWire | BengalsWire | BillsWire | BroncosWire | BrownsWire | BucsWire | CardsWire | ChargersWire | ChiefsWire | ColtsWire | CommandersWire | CowboysWire | DolphinsWire | EaglesWire | FalconsWire | GiantsWire | JaguarsWire | JetsWire | LionsWire | NinersWire | PackersWire | PanthersWire | PatriotsWire | RaidersWire | RamsWire | RavensWire | SaintsWire | SeahawksWire | SteelersWire | TexansWire | TitansWire | VikingsWire | DraftWire | TouchdownWire | ListWire | High schools
This article originally appeared on Sportsbook Wire: Detroit Lions at Buffalo Bills odds, picks and predictions
Our editors independently choose our recommendations. Some content is produced with paid support from a third party, however our editorial decisions remain independent. If you buy through our links, the USA TODAY Network may earn a commission. Prices and availability may change.
Gannett may earn revenue from sports betting operators for audience referrals to betting services. Sports betting operators have no influence over nor are any such revenues in any way dependent on or linked to the newsrooms or news coverage. Terms apply, see operator site for Terms and Conditions. If you or someone you know has a gambling problem, help is available. Call the National Council on Problem Gambling 24/7 at 1-800-GAMBLER (NJ, OH), 1-800-522-4700 (CO), 1-800-BETS-OFF (IA), 1-800-9-WITH-IT (IN). Must be 21 or older to gamble. Sports betting and gambling are not legal in all locations. Be sure to comply with laws applicable where you reside. It is your sole responsibility to act in accordance with your local laws.
Gambling involves risk. Please only gamble with funds that you can comfortably afford to lose. While we do our utmost to offer good advice and information we cannot be held responsible for any loss that may be incurred as a result of gambling. We do our best to make sure all the information that we provide on this site is correct. However, from time to time mistakes will be made and we will not be held liable. Please check any stats or information if you are unsure how accurate they are. No guarantees are made with regards to results or financial gain. All forms of betting carry financial risk and it is up to the individual to make bets with or without the assistance of information provided on this site and we cannot be held responsible for any loss that may be incurred as a result of following the betting tips provided on this site. Past performances do not guarantee success in the future and betting odds fluctuate from one minute to the next. The material contained on this site is intended to inform, entertain and educate the reader and in no way represents an inducement to gamble legally or illegally or any sort of professional advice.
Prediction Markets: Certain prediction markets are event contracts regulated by the U.S. Commodity Futures Trading Commission (CFTC) or other applicable regulatory authorities and are legally distinct from traditional gambling and sports betting. Eligibility requirements to participate in prediction markets differ from those for sports betting and gambling — you may be required to be 18 or older (or such other age as the applicable platform requires) and to satisfy other eligibility criteria established by the relevant platform and governing law. Prediction market trading involves financial risk and may not be available in all jurisdictions. The legal and regulatory status of prediction markets varies by jurisdiction and by platform. It is your sole responsibility to confirm that participation is lawful where you reside and to comply with all applicable laws and platform terms.
