The Bills are 9.5 point favorites this week according to Caesars Sportsbook as the team prepares to face the Detroit Lions at Ford Field in the Detroit.
Here's a list of game predictions from NFL analysts.
This has the makings of a game with a lot of offense. Both teams can score, but the Bills can really score. They will put up a big number here as Josh Allen wins a second straight game in Detroit after beating the Browns last week in the same building. The track is fast and the Bills can fly. The Lions won't keep up.
Prediction: Bills 40, Lions 23
The Bills had some experience adjusting to Ford Field. Although Josh Allen continued to slump, they had to be pleased about getting the traditional running game going and also spreading the ball around more effectively in the passing game. The Lions' young defense has played much better of late and made some big plays, but they struggle to multiple, diverse offenses.
Jared Goff hasn't played all that well during the Lions' winning streak and the negative game script will take them out of sticking with the run. Allen has his best game in a month in a complete road rout in a familiar venue.
Pick: Bills win 31-20 and cover the spread.
The Lions went into their Week 6 bye ranked dead last -- by a healthy margin -- in defensive efficiency (DVOA) through five games. In the five games since, they are 14th. Progress! The effort is there. Detroit can slow down a Buffalo team trying to simplify life for Josh Allen, and the Lions' offensive line can lean on the Bills enough to make this an entertaining game. That's all we ask for, Lions!
Prediction: Bills 30, Lions 23
Bills (-9.5) at Lions
MDS's take: The annual Detroit Thanksgiving bloodbath may not be quite as ugly for the home team this year, as the Lions are riding a three-game winning streak. But it's awfully tough to imagine them beating the Bills.
MDS's pick: Bills 20, Lions 13.
Florio's take: The Lions will try to feast on kneecaps before turkey. If it was anyone but the Bills, that three-game winning streak would have a great chance of extending to four.
Florio's pick: Bills 27, Lions 20.
The Thanksgiving Day triple-header begins with a fun one. The Bills, forced out of Buffalo by a blizzard, played in Detroit last week and ran for 171 yards in a victory over the Browns. But it was a competitive game, and Cleveland produced 27 first downs and 396 yards of offense.
The Lions, meanwhile, are coming off three straight wins, including an impressive 31-18 road victory against the Giants last week. The on/off splits with wide receiver Amon-Ra St. Brown are pretty wild. With St. Brown, they've performed like the second-most efficient offense in the league in terms of expected points added (EPA) per play. Without him, they've operated like the worst offense in the NFL. There's obviously some noise there, but still, he's been a legit difference-maker.
The Lions are playing at home, and their offense can move the ball. If you're not going to bet on Jared Goff to cover on Thanksgiving, what's the point of even celebrating the holiday?
The pick: Lions (+9.5)
What to watch for: After a 1-6 start, the red-hot Lions are trying to extend a rare three-game win streak in their first nationally televised matchup of the season. But the Bills are one of the toughest teams in the league and are already familiar with Ford Field, having just played in the Motor City after a snowstorm forced them to switch sites in Week 11. The holiday showdown could be a shootout with both teams ranked in the top six in points per game, yards per game and yards per play through 10 contests. -- Eric Woodyard
Bold prediction: Bills quarterback Josh Allen will have a full get-right game, throwing for 300-plus yards and rushing for at least 50 more. After a bumpy first half against the Browns, he had a strong second-half performance in the win, completing 81.8% of his passes and throwing for 10.3 yards per attempt. The Lions' defense has allowed the most yards per game (415.9) and per passing attempt (8.1) in the NFL. The Bills' offense began moving in the right direction over the final two quarters Sunday, and playing the Lions will be a big opportunity for a complete performance. -- Alaina Getzenberg
What to know for fantasy: Buffalo running back Devin Singletary has reached 15 fantasy points three times this season, and two of those instances have come in the past two weeks. He has 133 total rushing yards (66.5 per game) and three rushing TDs over his past two games.
Betting nugget: Since 2004, Detroit is 3-11 against the spread and 0-14 outright as an underdog on Thanksgiving. Detroit's last upset win on Thanksgiving happened in 2003 against Green Bay (+7).
Moody's pick: Bills 31, Lions 20
Walder's pick: Bills 34, Lions 17
The Buffalo Bills are on their way to Detroit again, this time to face the Lions on Thanksgiving. Check out the best travel photos presented by Imagine Staffing.
I'm not going to overthink this one. The Bills are producing 7.6 more points per game than expected based on the down, distance and field position of each play both for and against them, per data from TruMedia. Only the Philadelphia Eagles and Kansas City Chiefs have been better this season. The Lions, meanwhile, are generating 6.2 fewer points per game than expected; only the Pittsburgh Steelers and Houston Texans have been worse this season.
Other underlying stats, like net success rate (the rate of down series that create either another first down or a touchdown) and net yards per play also heavily favor Buffalo.
Neil's Pick: Buffalo Bills -9½