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NFL Week 16 game picks and predictions

This week’s NFL slate features several good interconference matchups, including 49ers vs Titans on TNF and Colts vs Cardinals on Christmas night. Read on for our picks and predictions for Week 16’s games!

Tennessee Titans v San Francisco 49ers Photo by Thearon W. Henderson/Getty Images

Week 16 of the 2021 NFL season is here! We’ve officially moved into the home stretch of the season, but COVID has started to rear its ugly head once again. Two games wound up delayed last week, and several teams were forced to scramble to replace key players on both sides of the ball. Hopefully things will improve this week, but I’m skeptical.

My hot streak of picks continued in Week 15 with my best outing to date: 12-4. That has helped bolster my record well above .500—72-54-1, to be exact—and I should be almost guaranteed to finish that way assuming I don’t blow it in epic fashion. Good thing I’ve never experienced that before. Read on for my picks and predictions for Week 16’s games!

All odds are taken from DraftKings Sportsbook and are subject to change. See the current odds here.

Thursday Night Football: San Francisco 49ers (8-6) at Tennessee Titans (9-5)

The pick: 49ers (-165)

Spread: 49ers -3 | Over/Under: 44.5 | Moneyline: 49ers -165, Titans +145

It’ll be hard to top last week’s electric TNF clash between Kansas City and Los Angeles, but this interconference matchup is also fairly spicy. A slumping and injury-ravaged Titans team takes on an ascending 49ers team that seems to finally be finding their footing. Tennessee has been horrid on offense since losing Derrick Henry, AJ Brown, and Julio Jones—as you’d expect. Meanwhile, San Francisco seems to be fully healthy once more, with Deebo Samuel and George Kittle playing at an elite level. I’ll take the 49ers on the road, where they’ve actually tended to play better.

Christmas Afternoon: Cleveland Browns (7-7) at Green Bay Packers (11-3)

The pick: Packers (-380)

Spread: Packers -7.5 | Over/Under: 45.5 | Moneyline: Packers -380, Browns +290

The Browns played fairly well with QB3 Nick Mullens at the helm, but that was against the Raiders. Even at full strength, it’s hard to see Cleveland keeping pace with a dynamic and dangerous Packers team that has dominated almost every opponent in their path.

Christmas Night: Indianapolis Colts (8-6) at Arizona Cardinals (10-4)

The pick: Colts (+100)

Spread: Cardinals -1 | Over/Under: 49 | Moneyline: Cardinals -120, Colts +100

Another spicy interconference matchup awaits, this time on Christmas night. While the Cardinals got taken down by the Lions in a poor performance, they still remain one of the better teams in the NFL. On the other side are the Colts, who have dug themselves out of a serious early-season hole to threaten the Titans for the AFC South crown. I like Indianapolis in the slight upset here.

New York Giants (4-10) at Philadelphia Eagles (7-7)

The pick: Eagles (-475)

Spread: Eagles -10 | Over/Under: 40.5 | Moneyline: Eagles -475, Giants +350

While the Eagles have been far from a complete team this season, they’ve proven to be pretty good at dispatching bad teams. The Giants weren’t particularly good with Daniel Jones, but without him they’re truly awful. Going with Philly in this one.

Los Angeles Rams (10-4) at Minnesota Vikings (7-7)

The pick: Rams (-155)

Spread: Rams -2.5 | Over/Under: 49.5 | Moneyline: Rams -155, Vikings +135

This looks like an exciting matchup between two of the NFC’s top Wild Card contenders. The Rams have recovered from a midseason slump and now face a hot-and-cold Vikings team on the road. Luckily, my foolproof method of predicting Minnesota’s games proved itself last week—so I’m sticking to it once again. Los Angeles wins this week based on my method (and also I think they’re the better team).

Buffalo Bills (8-6) at New England Patriots (9-5)

The pick: Bills (+120)

Spread: Patriots -2.5 | Over/Under: 43.5 | Moneyline: Patriots -140, Bills +120

An extremely important rematch awaits for the Bills and Patriots, as the winner will take control of the division crown and control their destiny the rest of the way. It’s tough to pick against the Patriots, but I don’t think they’ll sweep a team as good as Buffalo. The Bills find a way to pull this one out, though I think it’ll be ugly.

Tampa Bay Buccaneers (10-4) at Carolina Panthers (5-9)

The pick: Bucs (-450)

Spread: Bucs -10 | Over/Under: 44 | Moneyline: Bucs -450, Panthers +340

It’s tough to say exactly what this Bucs team will be without Chris Godwin and Leonard Fournette—and possibly Mike Evans—but I still think they’re better than a moribund Panthers team.

Jacksonville Jaguars (2-12) at New York Jets (3-11)

The pick: Jets (-110)

Spread: Jets -0 | Over/Under: 41 | Moneyline: Jets -110, Jaguars -110

A true pick ‘em line, the first I’ve seen all season, awaits for the Toilet Bowl matchup between the Jets and Jaguars. The league’s worst scoring offense meets the league’s worst scoring defense in a battle of the stoppable force vs. the movable object. Someone has to win this game, I guess? I’ll go with the Jets at home, who did put up an admirable fight against the Dolphins last week.

Detroit Lions (2-11-1) at Atlanta Falcons (6-8)

The pick: Falcons (-250)

Spread: Falcons -6 | Over/Under: 43 | Moneyline: Falcons -250, Lions +200

I’m honestly pretty shocked the Falcons are favored by 6 points in this one, but bettors are clearly not buying into the Lions surprising upset of the Cardinals last week. Despite all of the Falcons flaws, they’ve generally shown the ability to beat teams of similar or lesser talent consistently. I think that continues this week—though I think it’ll be closer than 6 points.

Los Angeles Chargers (8-6) at Houston Texans (3-11)

The pick: Chargers (-475)

Spread: Chargers -10 | Over/Under: 46 | Moneyline: Chargers -475, Texans +350

The Chargers were so close to pulling off the upset victory over the Chiefs last week. Even though they fell short, they proved that they can hang with the AFC’s best. The Texans have been a competitive opponent in recent weeks, but Los Angeles takes care of business.

Baltimore Ravens (8-6) at Cincinnati Bengals (8-6)

The pick: Bengals (-140)

Spread: Bengals -2.5 | Over/Under: 36.5 | Moneyline: Bengals -140, Ravens +120

The Bengals dominated the Ravens the last time these two teams played. I’m not sure the exact situation at QB for Baltimore, but either way the game will be close. Can Cincinnati take control of the division this week and complete the sweep over their rival? I think so.

Chicago Bears (4-10) at Seattle Seahawks (5-8)

The pick: Seahawks (-275)

Spread: Seahawks -6.5 | Over/Under: 43 | Moneyline: Seahawks -275, Bears +220

Seattle has fallen out of playoff contention with their loss to the Rams, but Pete Carroll is quite possibly coaching for his job at this point. A similar situation exists in Chicago, where Matt Nagy is on the hottest seat in the league. These are two deeply flawed teams, but I’d take a limited Russell Wilson over Matt Nagy’s offense any day of the week.

Denver Broncos (7-7) at Las Vegas Raiders (7-7)

The pick: Broncos (-110)

Spread: Raiders -1 | Over/Under: 41.5 | Moneyline: Raiders -110, Broncos -110

This one is tough to pick, as I’m currently unsure who will suit up at QB for Denver—though it seems most likely to be Drew Lock. Even if it is Lock, the Raiders don’t exactly inspire confidence after mustering just a 2-point win over the third-string QB of the Browns last week. I’ll take Denver’s rushing attack and defense here in what’s probably going to be a very ugly game.

Pittsburgh Steelers (7-6-1) at Kansas City Chiefs (10-4)

The pick: Chiefs (-350)

Spread: Chiefs -7.5 | Over/Under: 44 | Moneyline: Chiefs -350, Steelers +270

There’s a lot of uncertainty surrounding the Chiefs after a rash of positive COVID tests took out most of their weapons (Travis Kelce, Tyreek Hill) and a number of defensive starters. However, there seems to be hope for at least some of them to return under the NFL’s more lenient return-to-play protocols. Either way, I think Mahomes and the Chiefs are red hot right now and will find a way to handle Pittsburgh.

Sunday Night Football: Washington Football Team (6-8) at Dallas Cowboys (10-4)

The pick: Cowboys (-475)

Spread: Cowboys -10.5 | Over/Under: 47.5 | Moneyline: Cowboys -475, WFT +350

Once again, questions around COVID cloud this matchup as WFT QBs Taylor Heinicke and Kyle Allen both missed last week’s game. It appears Heinicke will return this week, but even if he’s back, the Cowboys are the heavy favorites here for a reason. I think Dallas takes care of business in primetime.

Monday Night Football: Miami Dolphins (7-7) at New Orleans Saints (7-7)

The pick: Saints (-160)

Spread: Saints -3 | Over/Under: 39 | Moneyline: Saints -160, Dolphins +140

It’s time to go back to the kiss of death this week, as I can’t stand watching the Saints win. The Dolphins deserve serious credit for pulling back to .500 after starting the season 2-7. They haven’t necessarily been dominant, but they’ve been getting it done against their schedule. The Saints are favored, but I’m hopeful that Miami finds a way to pull off the upset.

Odds/lines subject to change. T&Cs apply. See for details.