Thursday Night Football Predictions Week 16 | TNF Picks & 49ers vs Titans Best Bets

Last Updated: Dec 25, 2021

The San Francisco 49ers will visit the Tennessee Titans in the NFL Week 16 edition of Thursday Night Football at 8:20 p.m. ET on the NFL Network.

Entering Week 16, the Titans and 49ers would both qualify for the NFL playoffs if the season ended today. However, while we are in December, there is still a lot of football left to play.

Although the upcoming Thursday Night Football game between the 49ers and Titans does not have direct playoff implications since they play in different conferences, neither team can afford to lose, as both teams sit just one game ahead of the chasing pack.

Thursday Night Football Prediction Week 16

The 49ers and Titans are two teams going in opposite directions. The 49ers are 5-2 in their past seven games following a sluggish start to the year while the Titans are 1-3 in their past four games after opening the season 8-2.

Injuries have played a significant role on either side. The 49ers suffered injuries to George Kittle and their backfield early on, but have since got back on track once their key assets began to get healthy and returned to the field.

Meanwhile, the Titans were more or less healthy in the first half of the season. However, they have since lost Derrick Henry and A.J. Brown, two of their best players on offense.

We know that when healthy, the 49ers are one of the best teams in the NFL. They have displayed that talent in the second half of 2021. However, for the Titans, they need to figure out how to win without their top rusher and wideout.

While Brown will be eligible to return from injured reserve for this Week 16 matchup against the 49ers, we don’t know if he will be healthy enough to do so. Brown is dealing with a chest injury.

Sportsbook Play of the Day

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If the 49ers are going to win on TNF, the key to victory will fall on the arm of Jimmy Garoppolo. Although the 49ers drafted his heir-apparent, Trey Lance, in last April’s Draft, Garoppolo has not only remained healthy this season, but he is also playing some of the best football of his career down the stretch.

If Garoppolo continues to throw the ball effectively while limiting the giveaways, he will have no issues exploiting the Titans’ secondary, one of the worst defensive backfields in the NFL.

I can’t go on without mentioning the 49ers’ defense. San Francisco’s defense looked like a shell of itself in the first half of the year, but they have gotten back on track amidst their 5-2 run. They should have no issue containing a Titans’ offense snake-bitten by injury.

Once fueled by a superior rushing attack and an efficient passing game, Tennessee’s offense is one-dimensional, struggling to score against above-average defenses.

For a Titans victory, they must step up on defense, especially in their secondary. While they can stop the run, they may have difficulty doing so facing Kyle Shanahan’s elite rushing scheme. Starting running back Elijah Mitchell will miss his third straight game, however, which means Jeff Wilson Jr. will handle the bulk of the carries alongside versatile playmaker Deebo Samuel.

Offensively, Ryan Tannehill must step up. Sure, he played well against the Jaguars in Week 14, but let’s face it, they were a Jacksonville team in the midst of turmoil surrounding one of the worst head coaching hires in NFL history, Urban Meyer, who has since been shown the door.

In the previous two games against the Patriots and Texans — yes, the Texans — Tannehill could not get out of his own way. He led his offense to 13 points in each of those losses.

The Titans only managed to put 13 points once again last week against the Steelers, with Tannehill throwing for just 153 yards and an interception.

If you can read in between the lines, I am all-in on the 49ers on Thursday night.

TNF Week 16 Pick: 49ers 26, Titans 21

Thursday NFL Betting Trends for 2021

  • The Over is 6-11.
  • The Underdog is 7-10 against the spread.
  • The Favorite is 14-3 on the moneyline.
  • The Home Team is 7-10.

*Anthony Cervino is 30-18 on his NFL Best Bets for 2021 for The Game Day.

Thursday Night Football Best Bets Week 16

*NFL gameday odds and lines are current as of 10 AM ET on Thursday, December 23.

TNF Best Bet: 49ers -3 (-110) at Caesars

Wager: 4 Units

I am all-in on the 49ers on TNF. They are the superior football team right now. The 49ers are 5-2 in their past seven games. In four of those wins, they managed to score 30+ points. In the other, they scored 26.

The Titans don’t have enough on offense to keep up, especially facing a stingy 49ers defense. You can score on the 49ers’ defense, but I just don’t believe the Titans have enough firepower on offense to do so.

This is a 49ers’ defense that held the Rams and Jaguars to 10 points apiece in two of the aforementioned five wins.

Check out more of our NFL Week 16 betting tips:

TNF Best Bet: OVER 44.5 Total Points (-110) at Caesars

Wager: 2 Units

I believe in the 49ers’ offense more so than Tennessee’s. However, the Titans are still fighting to hold on to first place in the AFC South. They will put up a fight and score enough points to keep the game close. What’s more, the Total is only set at 44.5 points. The 49ers have scored over 30 four times in their past seven games.

If the 49ers drop another 31 points on Thursday night, then we only need 14 from the Titans to cover this bet.

TNF Best Bet: 49ers Moneyline (-160) at Caesars

Wager: 4 Units

This moneyline will likely be favorable enough to bet on its own without having to use it as a leg on a parlay to return solid value. I am all-in on the 49ers here.

Thanks for reading our NFL Week 16 TNF Predictions! For more NFL betting tips, check out our NFL Week 16 Best Bets and NFL Week 16 Prop Bets.


Anthony Cervino

Anthony Cervino is an NFL Writer and Betting Analyst for The Game Day. He is also a lifelong NFL savant and self-proclaimed league historian. In the industry, Anthony has excelled in both the fantasy football and sports betting space with fantasy his proverbial bread and butter. Anthony has made appearances on SiriusXM, amongst other publications. He is also the co-creator of the FF Faceoff (Faceoff Sports Network) and the FF Faceoff Mental Health Podathon partnered with the Hayden Hurst Foundation. Industry Clout: 15th most accurate ranker in the FantasyPros ECR for both draft and in-season accuracy (2019) | 8th most accurate ranker in the FantasyPros ECR for sleepers (2020) | 13th most accurate ranker in the FantasyPros ECR for in-season accuracy, including 2nd at quarterback and 3rd at tight end (2021).

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