49ers vs Lions Predictions Week 1 – NFL Pick, Best Bets & Parlays for San Francisco vs Detroit

Last Updated: Sep 10, 2021

49ers vs Lions Predictions Week 1 - NFL Pick of the Day

The 2020 NFL season was one to forget for the San Francisco 49ers and the Detroit Lions. While both clubs concluded the year with treacherous records — 6-10 and 5-11, respectively — their finishes were bleak for different reasons. Although one game separated the 49ers and Lions, they aren’t actually as close as their 2020 marks would suggest.

For the 49ers, they were once again decimated by injury last season. Players that include QB Jimmy Garoppolo, TE George Kittle, WR Deebo Samuel, CB Richard Sherman, and DE Nick Bosa all missed at least eight games.

The Lions were simply the Lions, though WR Kenny Golladay did miss 11 games and QB Matthew Stafford was far from healthy, playing through multiple ailments including a right thumb ligament tear, an injury to his rib cartilage and a sprained ankle.

The bigger issue was the culture — one that former HC Matt Patricia failed to build. The players simply did not buy into the Patriots’ way he tried to bring to Detroit.

Now, it’s 2021 — the dawn of a new season for two teams trending in two different directions. The 49ers are healthy and have Super Bowl aspirations, while the Lions are once again starting from the bottom floor with a new general manager, head coach, and quarterback.

Today, I will give you my best bets, picks, and parlays for the 2021 NFL Week 1 matchup between the 49ers and the Lions at Ford Field on Sunday, September 12 at 1:00 p.m. ET.

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San Francisco 49ers vs Detroit Lions Prediction

When toe meets ball for the opening kickoff in the 49ers-Lions match-up, Detroit-faithful will see a team that looks very different on the field — most notably on the offensive side of the ball.

I had already noted the fact that the Lions added a new head coach (Dan Campbell) and general manager (Brad Holmes), but didn’t dig into the quarterback change or other player personnel changes.

For the first time since 2009, someone other than Matthew Stafford is the projected Week 1 starter. This time, it’s former Los Angeles Rams QB Jared Goff.

In addition to Stafford’s departure, the Lions also have a brand new wide receiver room. Marvin Jones Jr., Kenny Golladay, and Danny Amendola all moved on with their careers and were replaced by Amon-Ra St. Brown, Breshad Perriman, and Tyrell Williams.

As underwhelming as Detroit’s passing attack sounds on paper, I expect OC Anthony Lynn to emphasize and ride the run behind presumed bell-cow D’Andre Swift and sidekick Jamaal Williams.

Last season, the Lions’ offensive line was underrated. With the addition of Penei Sewell, Pro Football Focus has them ranked as the 10th best unit entering 2021. If the Lions can successfully run the ball and control the tempo of the game, Kyle Shanahan’s offense will remain on the sidelines. Easier said than done.

Though I do expect the 49ers’ defense to regress sans former DC Robert Saleh and CB Richard Sherman, they will still be a solid unit under first-time DC DeMeco Ryans, who coached under Saleh since 2017.

In 2020, the 49ers’ defense surrendered the 17th most PPG (24.4), an average that should trend in the right direction this season so long as San Francisco’s defense can remain healthy.

Even if the 49ers’ defense doesn’t improve for the duration of 2021, they will appear better in the season opener. They will face a Lions offense that is coming off a campaign in which they averaged a lackluster 23.6 points per game with a unit that looks better on paper than the projected starting lineup for 2021.

The difference in this game will ultimately come down to coaching, as well as an outright overmatch in talent. At full health, the 49ers have the better roster and head coach. It is not close. Whether it is Jimmy Garoppolo or Trey Lance under center for the 49ers, expect Shanahan’s offense to come out on fire.

Barring injury, the 49ers will have Garoppolo, Kittle, Samuel, Brandon Aiyuk, and Raheem Mostert all on the field together for the first time since early 2020. Let’s not gloss over the addition of Trey Sermon, either. A rookie third-round pick, Sermon could take over this backfield if he is the real deal.

Last year, the Lions had the worst defense in football, allowing a league-high 32.4 PPG. With a new defensive coordinator in Aaron Glenn, I don’t see too much early improvement, which bodes well for the 49ers’ expected offensive output.

Betting Pick: San Francisco 49ers 30, Detroit Lions 20

Trey Lance, QB, San Francisco 49ers

Will Trey Lance see some action when the San Francisco 49ers take on the Detroit Lions in Week 1 of the 2021 NFL season?

San Francisco 49ers vs Detroit Lions Best Bets

Best Bet: 49ers -7.5 (-105 at BetMGM)

I looked at DraftKings (-8), BetRivers (-8), and BetMGM (-7.5) to see which one had the best odds for this 49ers-Lions encounter. By far, BetMGM was the winner. The fact that BetRivers opened by giving the 49ers 8.5 points tells me I am not crazy to foresee a San Francisco blowout on the road.

The Lions will be a tough team and a tough out, but they will be outmatched by teams with more talent more times than not in 2021. We will catch a glimpse of this in Week 1.

I love the 49ers giving 7.5 points in the season opener. They will easily cover.

  • Both the 49ers and Lions went 7-9 against the spread last season.
  • The 49ers went 3-3 ATS in their final six games.
  • The Lions went 3-2 ATS in their final five games.
  • The 49ers are 4-2-1 ATS in their last seven games against the Lions.

Best Bet: Over 45.5 (-110 at BetMGM)

The Lions will try to control the pace of the game by running the football. However, they could be stifled early, as the 49ers yielded the seventh-fewest rush yards per game (106.4) last season.

And even if the Lions can get something going, it will only be a matter of time until San Francisco’s high-octane offense hangs points in bunches on Detroit’s horrendous defense, which will force the Lions to pass.

The 49ers are no stranger to Jared Goff, or the fact that the former No. 1 pick struggles under duress. Goff giveaways translate to additional drive opportunities for the 49ers’ offense.

45.5 points is a low point total, but it is fitting. The Lions’ offense is projected to be one of the worst in the NFL. However, the same can’t be said about the 49ers when Shanahan has a healthy starting quarterback and a half-healthy supporting cast (at worst).

The 49ers will have no problem hanging 30 on the Lions. All the Lions need to do is find 17 points to help cover the over.

  • The Lions and their opponents combined to score at least 46 points in 14 of 16 games in 2020.
  • The 49ers and their opponents combined to score at least 46 points 6 of 16 games in 2020.
  • The over is 2-4-1 in the last seven meetings between the 49ers and Lions.
  • The over is 5-2 in the last seven games in which the 49ers were favored and 4-0-1 in their last five as a road favorite.
  • The over is 8-2 in the Lions’ last 10 games as an underdog.
  • The over is 13-3 in the Lions’ last 16 games in Week 1.

Best Bet: 49ers Moneyline (-350 at BetMGM)

I don’t normally recommend taking a wager with these types of odds, as you need to lay a lot to win a little. However, this is nearly a lock. I don’t give the Lions a shot unless the 49ers completely fall flat on their face.

The best way to take advantage of the 49ers’ Week 1 moneyline is to include it into a same-game parlay or a parlay in general.

San Francisco 49ers vs Detroit Lions Same Game Parlay Picks

I will keep it simple with my same-game parlay at DraftKings Sportsbook and use two of my best bets and parlay them for a solid return. It’s Week 1, and I am not going to go too crazy with my parlay builds. It is about bankroll building for me right now. The 49ers giving 7.5 and over 45.5 should both hit.

  • 49ers -7.5 (-105) at BetMGM
  • Over 45.5 (-110) at BetMGM


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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