San Francisco 49ers vs. Tennessee Titans Pick – NFL Week 16

Two days after the conclusion of Week 15, we’re already onto Week 16 with Thursday Night Football in Nashville.

The San Francisco 49ers are looking to stay hot following their fifth win in their previous six attempts. In their most recent win, the 49ers cruised past the Atlanta Falcons for a 31-13 win in Santa Clara.

The Falcons had no concept of how to finish in the red zone. They were stopped on 4th down on several drives in the loss.

That’s a credit to the 49ers’ defense for tightening up when it was required. It wasn’t just a case of the Falcons shooting themselves in the foot time and time again.

The most impressive aspect of the win was that the 49ers didn’t have a letdown after their gritty overtime win at Cincinnati last week.

San Francisco walked off the Bengals with a touchdown in Cincinnati for a big 26-23 win. The Niners haven’t been only beating up on bad teams during this hot run.

A 31-10 win over the Los Angeles Rams on November 15 is what kickstarted the fun times for the 49ers in the Bay Area. They are up to a record of 8-6 five games later.

Don’t they say it’s all about getting hot at the right time? If the playoffs started today, the 49ers aren’t a team I’d want to see on the docket as an opponent.

The Titans will attempt to cool the 49ers off at home in Nashville under the lights. It’s a big game for the Titans after a physical loss versus the Pittsburgh Steelers at Heinz Field, 19-13.

Tennessee desperately needs Derrick Henry back on the field. The offense continues to struggle without Henry. Ryan Tannehill’s flaws are being exploited without Henry present.

Defensive coordinators are finding it much easier to prepare for the Titans with Henry off the field. That’s going to happen when one of the best running backs in the league isn’t active.

Tannehill is making the big bucks now, though. For the money he’s paid, there are high expectations for him. That includes coming up with plays when there isn’t a star running back to lean on.

Head below for our free 49ers vs. Titans pick on December 23, 2021.

San Francisco 49ers vs. Tennessee Titans Betting Odds and Team Statistics:

The following odds are courtesy of BetOnline:

Teams Spread Moneyline Total
San Francisco 49ers -3.5 (-115) -181 Over 44.5 (-110)
Tennessee Titans +3.5 (-105) +161 Under 44.5 (-110)
Team Data San Francisco 49ers Tennessee Titans
Overall Record 8-6 9-5
ATS Record 7-7-0 8-6-0
Away/Home Record 5-2 5-2
ATS Away/Home 4-3-0 4-3-0
Points Per Game 32.2 31.8
Points Against Per Game 25.7 24.1
Passing Yards Per Game 240.0 202.8
Rushing Yards Per Game 126.6 142.3

49ers vs. Titans Prediction:

Ryan Tannehill has to stop worrying about the absence of Derrick Henry and begin making plays with his arm. Tannehill is going into Thursday night with 3,118 yards, 14 touchdowns, and 14 interceptions on 66.2% completions.

That doesn’t look like a guy who is on a four-year $118 million deal. The Titans just signed the deal this past summer, so this isn’t the end of his contract or anything.

There could be serious buyer’s remorse for the Titans now. Tannehill has the Titans’ offense in 17th with 345.1 yards per game. Despite no Henry, it’s the running game carrying the weight.

The Titans have recorded 142.3 yards per game for fourth in the NFL. However, the passing game has struggled, with just 202.8 yards per game through the air.

Along with the lack of yards and points from Tannehill, he is turning the ball over with 14 interceptions going into Thursday night. If the Titans are going to beat the 49ers, it’s going to come through the air against the 49ers’ secondary.

San Francisco is dealing with injuries on the backend of their defense, though this unit has been holding up pretty well. The 49ers are seventh in the NFL, with an average of 213.2 yards allowed through the air per game.

San Francisco 49ers vs. Tennessee Titans Betting Trends:


  • 5-1 ATS in their previous six games
  • 4-1 ATS in their previous five games as a betting favorite
  • 4-1 ATS in their previous five games as a betting favorite on the road
  • 5-2 ATS in their previous seven games versus a team with a winning record
  • 6-2 overall in their previous eight games on the road


  • 1-4 ATS in their previous five games
  • 2-6 ATS in their previous eight games on Thursday Night Football
  • 5-15-1 ATS in their previous 21 games in Week 16
  • 1-4 overall in their previous five games versus the 49ers at Nissan Stadium
  • 1-4 ATS in their previous five games in December

Jimmy Garoppolo has been smart in that he’s getting the ball out to his playmakers. He isn’t making things complicated on himself, which is the smart thing to do when there’s George Kittle and Deebo Samuel on the field.

Kittle has been going on a tear and isn’t due to stop in Nashville on Thursday night. He’s recorded 181, 151, and 93 yards in his last three outings. There’s a guy that is playing like he wants to go to the playoffs. He and Jimmy G have been hooking up often.

Garoppolo has passed for 3,172 yards, 18 touchdowns, and 8 interceptions on 67.4% completions. He’s been steady recently with 531 yards and 3 touchdowns versus the Bengals and Falcons. Note that Garoppolo has had only one multi-interception game in his last eight starts.

The 49ers are well-balanced, with a running game that is capable of producing as well. They are seventh in the NFL, averaging 126.6 yards per game on the ground. The 49ers have been unique, with Samuel playing a utility role as a running back and receiver. Preparing for Samuel on sweeps can be tough.

At first glance, you look at the points and want to take the Titans in primetime at home. Then you look at Tannehill and wonder if he can lead the Titans to enough points in this one. My confidence in Tannehill is low without Henry on the field.

The 49ers look like the play following a physical game for the Titans last week. San Francisco didn’t break a sweat, while the Titans were getting pushed around, and now they’re on a short week. I’d give a look at the 49ers to win by a touchdown on the road for another big win.


49ers vs. Titans Pick
Kyle E / Author

Kyle is a veteran of TheSportsGeek and has spent nearly a decade providing accurate sports picks and writeups here. He has been a sports handicapper for 10+ years and started sharing his picks and thoughts in 2011 at TheSportsGeek. His expertise spans across multiple sports, including the NFL, NCAAF, MLB, NHL, and horse racing. Prior to writing for TheSportsGeek, Kyle was a fantasy football expert, who ultimately parlayed it into a successful sports betting career. You can find his picks daily only at TheSportsGeek.

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