NFL Picks Against the Spread: ATS Predictions for Every Week 16 Game

We're getting down to the nitty-gritty in the regular season as I offer my NFL picks against the spread for Week 16. 

This week's picks feature the Los Angeles Chargers, Detroit Lions, and San Francisco 49ers as I dole out a 5-star selection. As part of the NFL predictions for Week 16, I've provided a prediction for every game on the slate.  

NFL picks against the spread: Week 16 ATS predictions

See all of our experts' NFL picks for Week 16 based on the latest NFL odds; pick confidence based on a 1-to-5-star scale.

My best ATS picks for Week 16

Chargers (+2) vs. Cowboys ⭐⭐⭐⭐⭐

No disrespect to the Cowboys, but I was gobsmacked to see them as the betting favorite for the matchup against the 10-4 Chargers. The Chargers have won six of the previous seven games, including the last three. 

They beat the defending Super Bowl champions at home despite Justin Herbert nursing an injury to his non-throwing hand, and then walked into Arrowhead Stadium and ended the Chiefs' playoff hopes. 

The Cowboys have lost two in a row, the last of which was at home as the 6.5-point betting favorite against the inconsistent Minnesota Vikings. In addition, star defensive tackle Quinnen Williams is in a race against time to suit up after entering concussion protocol. 

You can get the Chargers at +1.5 or +2. I'm going with the former, as I don't think the visitors need any buffer, and I'm not concerned about the prospect of a push. BetMGM and FanDuel offer the best price (-105), and a winning $10 bet will profit $9.52. 

Lions (-6.5) vs. Steelers ⭐⭐⭐⭐

This isn't a great matchup for the Steelers, who enter on a short week after dispatching the Miami Dolphins on the tundra of Acrisure Stadium. T.J. Watt didn't feature in the Steelers' Week 15 victory, and it's unclear whether he'll get the green light for the game at Ford Field.

Playing at home tilts the balance in Detroit's favor. Not only is their season on the line, but the Lions' offense usually performs at its peak in the perfect conditions of Ford Field.

I also believe Jahmyr Gibbs has a favorable matchup against a Steelers defense that allowed 466 rushing yards to the Buffalo Bills and Baltimore Ravens before neutralizing De'Von Achane in arctic-like conditions. Gibbs' success will open up play action for Jared Goff and Co. 

BetMGM offers the best value (-114) and will pay a profit of $8.77 on a winning $10 bet. 

49ers (-5.5) vs. Colts ⭐⭐⭐⭐

While the Colts, most notably Philip Rivers, performed admirably against the Seattle Seahawks, I'm not buying that they can stick with th sizzling-hot and mostly healthy San Francisco 49ers. 

The 49ers are 4-0 since Brock Purdy's return, winning each game by at least 11 points. Their average margin of victory since his return is 15.25 points. Both sides of the ball are playing at a high level, and Lucas Oil Stadium offers conditions that are ideal for another productive offensive outing. 

Rivers' fairytale return to the NFL might more closely resemble a nightmare after the glimmer of his first game back has well and truly faded, particularly as the 49ers will be planning to defend a predictable, rush-heavy defense.

The best sports betting sites are offering -5.5 or -6 for the 49ers. I'm going with the best value at the former, provided by BetMGM. Its -118 odds imply a 54.13% probability, and a winning $10 bet will profit $8.47.