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Titans vs. Bills Picks, Predictions NFL Week 2: Tennessee Covers Disrespectful Spread

Top NFL picks for the Week 2 Monday Night Football matchup between the Titans and Bills.
Mike Spector
Mike Spector

Last Updated: October 8, 2025 11:12 AM EDT • 4 minute read

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The Buffalo Bills and Tennessee Titans meet on Monday Night Football for the second consecutive year. We’re breaking down the betting aspect with our Titans-Bills picks.

There was arguably no bigger statement made in Week 1 than Buffalo’s 31-10 victory over the defending Super Bowl champion Los Angeles Rams. Oddsmakers took notice as the Bills’ Super Bowl odds plummeted from +700 to +450 after the victory.

Next up is a Titans team that won an AFC-best 12 games last year but was stunned by the New York Giants in Week 1 after their potential game-winning field goal with no time left went wide.

Here are our Titans-Bills NFL picks for Week 2 (odds via PointsBet, DraftKings Sportsbook, Caesars Sportsbook; pick confidence based on a 1-to-5-star scale).

Titans vs. Bills Game Info

Date/Time: Monday, Sept. 19, 7:15 p.m. ET
TV: ESPN/ESPN2
Location: Highmark Stadium, Orchard Park, NY
Weather: 57 degrees, 24% chance of precipitation, 12-mph WSW wind

Check out our Titans-Bills same-game parlay picks here.

Titans vs. Bills Odds Analysis

The line has teetered between Buffalo -9.5 and -10. The Bills have been popular favorites, attracting 84% of the tickets and 81% of the cash.

The total has been much more volatile than the point spread, moving as much as two points from 49.5 down to 47.5. Sharps have pounded the Under, as just 45% of the tickets, but 81% of the cash has landed on that side.

Titans vs. Bills Picks

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Titans vs. Bills ATS Pick

Titans +10 (-107) ★★★★★

This line feels disrespectful to Tennessee, the No. 1 seed in the AFC last year, after one bad week. A big line was to be expected, especially with NFL fans everywhere getting to gush over Buffalo’s Week 1 performance as a standalone game to kick off the season last Thursday night.

It is rare for non-division rivals to face each other as much as the Titans and Bills have recently, with the two playing every year since 2018. Tennessee and Buffalo have split those matchups, though the Titans have won the last two by a combined 29 points. 

Since the start of 2021, Tennessee has allowed 35.9% of third-down conversions, fourth-best in the NFL. That should slow down the Bills somewhat and give Titans quarterback Ryan Tannehill and Co. a chance to play a ground-and-pound style with running back Derrick Henry to keep Buffalo’s offense off the field.

If Tennessee’s late kick against the Giants went through the uprights last week, we would potentially be looking at a line of -7 or lower. Do not fall into the oddsmakers’ temptations to think Buffalo will roll in this game, as getting double-digits with the Titans should be an automatic play.

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Titans vs. Bills O/U Pick

Over 47.5 (-107) ★

The Bills have not punted the ball in four of their last six games, including the playoffs. Quarterback Josh Allen is coming off his seventh career game with at least three passing touchdowns and a rushing touchdown, which already ranks third all-time. 

We are not as confident on this play as we are on the point spread, given how much of a difference-maker Von Miller was for the Bills defense. Miller finished with two sacks and three tackles for loss, and Buffalo pressured Matthew Stafford on 31% of his dropbacks despite blitzing just one time. In addition, Buffalo’s seven sacks tied a franchise record for a season opener. 

It is unlikely the Titans will shut down this explosive Bills offense, so if they cover the spread, it will come as part of a high-scoring game.

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Titans vs. Bills Prop Pick

Henry to score a TD (+115) ★★★

Henry ran for 143 yards and 7.2 yards per carry in last year’s MNF matchup against Buffalo, and the Bills have concerning injuries on the defensive line, with Tim Settle questionable and Ed Oliver ruled out.

Henry has spiked the ball six times in four career games against the Bills, making plus-odds on this wager a steal.

Where to Bet on Titans vs. Bills Picks

Here are our top-rated sportsbooks:

SEE ALSO: All picks, odds, and sports betting news. Be sure to check out SportsbookReview.com’s community forums and betting tools.

Titans-Bills picks made 9/18/2022 at 6:09 a.m. ET

Written by:
Mike Spector
Mike started in the sports writing industry in July 2019, and gained a lot of followers in his first year after finishing with the No. 2 overall record in an annual NFL betting competition, which made picks against the spread, and from an Over/Under and moneyline perspective. Mike is an avid fan of the NFL, MLB, tennis, and all college sports. In his opinion, March Madness is the best sporting event there is, and he's especially euphoric starting with conference tournament time in college basketball. Mike's a big advocate of "fading the public" and making plays that are contrarian, constantly citing that "there are reasons why they have those big shiny buildings in Las Vegas." When making wagers, Mike leans on his NFL experience and always scours the best odds at all of the major sports betting sites, where he mostly sifts through DraftKings, FanDuel, BetMGM, and bet365. He's tried several others and is of the firm belief that bettors should not just stick to one sportsbook, as there is always likely better value to be had with the same wager. In addition, while Mike received his undergraduate degree from Villanova University, he has no issue betting against the Wildcats when it comes to college basketball wagering, and suggests other bettors should always put their “head” before their “hearts.”