The NFL is hitting its stride — and you don’t have to take my word for it. We’re coming off what could be remembered as the game of the year, when the Seattle Seahawks stormed back to defeat the Los Angeles Rams in overtime on Thursday night. That comeback officially locked Seattle into the playoffs and set the stage for a Week 16 slate packed with postseason implications.

As the action continues, several teams enter the weekend with win-and-in scenarios. The New England Patriots and San Francisco 49ers can clinch playoff spots simply by taking care of business. The Philadelphia Eagles can secure the NFC East with a victory, while several other teams will be scoreboard-watching, hoping a little help pushes them over the line. The result is a Week 16 schedule that’s as compelling to bet as it is to watch.

With a Saturday doubleheader kicking things off, now’s the time to get your wagers in order. Below are our best bets and game-by-game picks for the remainder of the Week 16 slate.

All odds courtesy of DraftKings Sportsbook.

New York Jets at New Orleans Saints

Sunday, 1 p.m. ET (CBS | Paramount+)

It appears the New Orleans Saints may have found their quarterback of the future. Tyler Shough has been outstanding in recent weeks, potentially positioning himself as the franchise’s starter heading into 2026. Through six starts, Shough is completing 69% of his passes with a 92.1 passer rating, and he’s guided New Orleans to back-to-back wins over division rivals Tampa Bay and Carolina.

This week, he faces a New York Jets defense that just surrendered six total touchdowns to Trevor Lawrence — a performance that ultimately cost defensive coordinator Steve Wilks his job. With that context, it’s difficult to see how undrafted rookie Brady Cook, making just his second career start, keeps pace.

Projected score: Saints 26, Jets 17
The pick: Saints -6.5

Tampa Bay Buccaneers at Carolina Panthers

Sunday, 1 p.m. ET (Fox | Fubo)

Neither team enters this matchup brimming with confidence after fourth-quarter collapses in Week 15, but the Tampa Bay Buccaneers appear to be in deeper trouble. Tampa Bay has dropped five of its last six games and allowed nearly 30 points per game during that stretch. The defense ranks near the bottom of the league in passing yards allowed and red-zone efficiency.

Quarterback Baker Mayfield has also struggled away from home, posting a 1–3 record in his last four road starts with more interceptions than touchdowns.

That points toward value on the Carolina Panthers, especially given their strong track record as home underdogs. Bryce Young has been far more effective at Bank of America Stadium, where he owns a 4–1 record this season with a 98.5 passer rating.

Projected score: Panthers 24, Buccaneers 21
The pick: Panthers +3

Jacksonville Jaguars at Denver Broncos

Sunday, 4:05 p.m. ET (Fox | Fubo)

Despite Trevor Lawrence’s eye-popping numbers during Jacksonville’s winning streak, it’s still difficult to fully buy into the Jacksonville Jaguars. Yes, Lawrence leads the NFL in yards per attempt and touchdown passes over the last five games — but much of that production came against struggling defenses, including the Jets.

This week is a different challenge entirely. The Denver Broncos boast one of the league’s most dominant defenses, recording 58 sacks this season and remaining a perfect 7–0 at home. Mile High has become one of the toughest venues in the NFL, and unless Jacksonville proves otherwise, skepticism is warranted.

Projected score: Broncos 24, Jaguars 20
The pick: Broncos -3.5

San Francisco 49ers at Indianapolis Colts

Monday, 8:15 p.m. ET (ESPN | Fubo)

The Indianapolis Colts surprised many last week, with 44-year-old Philip Rivers nearly engineering an upset against Seattle. That performance felt more like a perfect storm than a sustainable trend, particularly with the Seahawks likely looking ahead to their Thursday night showdown with the Rams.

Expect the San Francisco 49ers to be fully locked in. Kyle Shanahan’s team has quietly emerged as a sleeping giant in the NFC, winning four straight games by double digits. Brock Purdy appears to be rounding into form, and San Francisco has been flawless in prime time this season.

Projected score: 49ers 30, Colts 19
The pick: 49ers -5.5