Bills vs. Chargers Prediction, Pick & Odds Week 16: Sunday Night Football

Josh Allen of the Buffalo Bills throws a pass against the Cincinnati Bengals, and we offer our top Bills vs. Chargers prediction based on the best NFL odds. — Josh Allen of the Buffalo Bills throws a pass against the Cincinnati Bengals. Photo by Bryan M. Bennett/Getty Images via AFP.

Two teams on different trajectories face off in a unique Saturday edition of Sunday Night Football. We’ve got you covered with our prediction for the Bills vs. Chargers game, based on the top NFL odds available.

In Week 16, NFL fans will have a special treat as the Buffalo Bills face off against the struggling Chargers on Saturday night instead of Sunday.

Even though many doubted the Bills’ chances in the Super Bowl odds for weeks, they are still fighting for a spot in the postseason and defeated the Dallas Cowboys in Week 15 to stay in the running for the NFL playoffs.

However, the Chargers (5-9) were recently crushed on Thursday Night Football. Consequently, they have dismissed their head coach and general manager, leading to a team in disarray entering this upcoming match.

Here is our top prediction for the Bills vs. Chargers Sunday Night Football game, along with our NFL Week 16 predictions and player props for the game. Our confidence level is rated on a 1-to-5-star scale, with odds provided by our top NFL betting sites.

Bills vs. Chargers prediction: Sunday Night Football

Bills team total Over 27.5 (-110 via Caesars) ⭐⭐⭐⭐

The most favorable option for this game was initially Chargers +14, but it quickly vanished. The value has now diminished for the home underdogs, and it still seems risky to bet on the Bills as nearly two-touchdown favorites on the road, especially considering their past disappointments in similar situations.

Instead, I am confident that Buffalo’s offense will continue to perform well against the struggling team in Los Angeles.

The Bills’ dominant 31-10 victory over the Cowboys last week caught the attention of the entire league, but it was just another impressive performance for their high-powered offense. Buffalo ranks second in offensive DVOA (22.8%) and EPA per play (+0.19), leading the league in third-down conversion rate (49.2%) and boasting top-five statistics in points per drive (2.47), drive success rate (43.3%), and red-zone touchdown percentage (67.3%). This highlights the unstoppable nature of the Bills’ offense.

The Bills’ offense has seen a significant boost under interim coordinator Joe Brady, ranking in the top five in scoring (29.3 PPG) and total offense (394 YPG) while scoring at least 31 points in three of four games. This improvement has also been accompanied by a resurgence from QB Josh Allen, who has risen in the NFL MVP odds due to his impressive dual-threat abilities. Check out more on Allen in King Orson’s Josh Allen player props.

In contrast, the Chargers are ranked 27th in defensive EPA per play (+0.01) and are among the bottom six in opponent points per game (24.6) and per drive (2.11). They have also faced challenges in creating turnovers, ranking 10th-worst in the percentage of opponent drives ending in a turnover (10.1%) and fifth-worst in defensive interception rate (1.4%).

Last week’s game against the Las Vegas Raiders was the breaking point, as the team allowed 63 points, the second-highest total of the season and tied for the seventh-highest in NFL history. As a result, the Chargers swiftly dismissed head coach Brandon Staley, known for his defensive expertise, and appointed outside linebackers coach Giff Smith as his replacement. This decision led to a reorganization of responsibilities among the entire defensive coaching staff.

Perhaps the team’s disorganization will finally solve their defensive issues, but it’s hard to ignore the absence of the Chargers’ key defenders all season long and the clear impact it has had. They now face their biggest challenge yet against one of the most high-powered offenses in the league. Best of luck to them.

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Bills vs. Chargers best odds

Caesars (-110)

DraftKings	FanDuel	BetMGM	Caesars	bet365
Over 27.5	Over 27.5	N/A	Over 27.5	Over 27.5
-112	-118	N/A	-110	-135

Our top sports betting apps are offering the Bills’ team total at 27.5 points, but prices vary. We recommend taking the -110 odds from Caesars, as they are currently the best available on the market compared to odds as short as -135 on the Over.

It is always beneficial to compare options at various sportsbooks, as the discrepancy between -110 and -135 equates to almost 17% of your initial bet. Additionally, don’t forget to explore our top sportsbook promotions to maximize your betting experience.

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Bills vs. Chargers odds for Sunday Night Football

Bills vs. Chargers odds analysis

Earlier, we noted that the Chargers initially started as 14-point underdogs. However, due to heavy betting activity, the line has shifted to favor the Bills by 11.5 to 12.5 points on our top sports betting sites.

There has been significant movement in the total this week, starting at 42 and rising to 44 at some of our top sportsbooks.

Sunday Night Football game info

When: Saturday, Dec. 23 at 8 p.m. ET
Where: SoFi Stadium, Inglewood, CA
How to watch: Peacock
Weather: Indoors

Prediction for Bills vs. Chargers made on Wednesday at 2:45 p.m. ET.

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Written By:
Morgan Xaviero

Morgan Xaviero is a publishing editor and lead writer for Underscoreg Review. An award-winning writer, reporter, and editor with a decade of sports media experience, “C-Jax” has worked with ESPN, Forbes, theScore, and various daily newspapers before joining the Underscoreg Review team. He’s a proud graduate of the University of North Carolina, where he served as a beat writer for the Tar Heels’ championship run through the NCAA men’s basketball tournament in 2017. Jackson has spent the last five years covering sports betting as a predictive analyst, features writer, and industry reporter. Since joining the team in 2026, he’s played a key role in Underscoreg Review’s coverage of the Super Bowl, March Madness, and NBA playoffs while serving as the lead writer for the growing WNBA and NASCAR betting scenes. Though he’s cashed some big bets over the years — including Lamar Jackson to win MVP (twice) — he’s still haunted by enough second-place bet slips to wallpaper his home office. While Jackson is a committed “process over results” bettor with a keen eye for advanced stats and subtle bias in futures markets, he also embraces sports betting as a vehicle for entertainment and personal investment. He’s written about everything from hot dogs to groundhogs and still hasn’t forgiven his “inside source” for a sabotaged bet on the Gatorade color in Super Bowl LV.