Dak Prescott Dallas Cowboys
Rookie quarterback Dak Prescott will start for the Dallas Cowboys in Week 1 in place of the injured Tony Romo. Getty

Making picks against the spread is never easy, but it might be most difficult when NFL teams have yet to play any meaningful games. Week 1 of the 2016 season is set to get underway on Thursday night with a Super Bowl 50 rematch, and 16 games in total are on the schedule.

The Seattle Seahawks and Kansas City Chiefs begin the year as the biggest favorites in Week 1, playing in the only games that feature a betting line of at least seven points. Five teams are favored by less than a field goal, and one game is a pick’em just days before kickoff.

Below are picks against the spread for every game in Week 1, as well as updated betting odds at Las Vegas and online sportsbooks. Betting lines and trends are courtesy of OddsShark.

Carolina Panthers (-3) at Denver Broncos

Thursday’s matchup will look a lot different from last season's Super Bowl. Cam Newton might not put up MVP numbers like he did most of last year, but he also won’t be sacked six times again. Trevor Siemian has never even started a regular-season game, and he could have a lot of trouble against a top defense on by far the biggest stage of his career.

Prediction ATS: Carolina

Tampa Bay Buccaneers (+3) at Atlanta Falcons

The Buccaneers beat the Falcons twice last year, and Tampa Bay should be better in 2016 as Jameis Winston enters his second season. Matt Ryan is one of the NFL’s most overrated quarterbacks, and the Falcons are 0-7 against the spread in their last seven games as favorites of three points or more.

Prediction ATS: Tampa Bay

Jameis Winston Buccaneers
Look for Jameis Winston and the Tampa Bay Buccaneers to start the 2016 NFL season with a win on the road. Getty

Minnesota Vikings (-2) at Tennessee Titans

Minnesota’s Super Bowl hopes took a hit with Teddy Bridgewater’s injury, but the Vikings are still a 10-win team. They might not be championship-caliber quarterbacks, but Sam Bradford and Shaun Hill are competent enough . The Vikings’ defense and running game is so good that the team won’t need much more than that to defeat the Titans, who could be headed for a last-place finish.

Prediction ATS: Minnesota

Cleveland Browns (+4) at Philadelphia Eagles

The Browns are probably the worst team in the AFC, but Philadelphia shouldn’t be favored by more than a field goal against anyone in the season opener. Carson Wentz gets his first ever NFL start, and his only preseason action resulted in him post a 41.8 passer rating. For all of Robert Griffin’s issues, he has a few years of experience, giving Cleveland a chance to pull off the Week 1 upset.

Prediction ATS: Cleveland

Cincinnati Bengals (-2.5) at New York Jets

The Jets overachieved with 10 wins in 2015, and they could have a tough time going .500 with Ryan Fitzpatrick likely returning to the mediocre quarterback that he’s been for most of his career. The Bengals went 10-3 with a healthy Andy Dalton, and they’ll be one of the AFC’s top teams now that the quarterback is healthy.

Prediction ATS: Cincinnati

Oakland Raiders (+1) at New Orleans Saints

The Raiders have become a bit of a trendy playoff pick, and with good reason. Last year’s exciting young offense should take a significant leap in 2016, and they’ll put up 30-plus points against the NFL’s worst defense from a season ago.

Prediction ATS: Oakland

San Diego Chargers (+7) at Kansas City Chiefs

Kansas City has owned San Diego in the last few years, winning four straight against the Chargers and going 4-1 against the spread in their last five head-to-head matchups. The Chiefs have a real chance to win the AFC West and go deep in the playoffs, and it starts with a big victory in Week 1.

Prediction ATS: Kansas City

Buffalo Bills (+3) at Baltimore Ravens

For as much trouble as they sometimes have later on in the season, Rex Ryan and the Bills usually get off to a good start. Buffalo is 9-2 against the spread in their last 11 Week 1 games, and Ryan is 6-1 in season openers with his only loss coming by one point. The Ravens should be better than they were last year, but they are still a notch below the Steelers and Bengals in the AFC North.

Prediction ATS: Buffalo

Chicago Bears (+6) at Houston Texans

The Bears won’t be as bad as they looked in the preseason, where they showcased an anemic offense. Brock Osweiler defeated Chicago by just two points with Denver a year ago, and Houston isn’t nearly as good as that Broncos team that won the Super Bowl.

Prediction ATS: Chicago

Green Bay Packers (-5.5) at Jacksonville Jaguars

With some of the NFL’s best young receivers and an improving quarterback, Jacksonville has the chance to put up a lot of points this weekend. Green Bay will probably win the season opener, but the Jaguars might keep a high-scoring game close and end it with a backdoor cover.

Prediction ATS: Jacksonville

Miami Dolphins (+10.5) at Seattle Seahawks

Seattle is the best team in the NFC, and they’ll reaffirm that belief on Sunday. The Seahawks have won their last seven home openers, with six of those victories coming by at least 20 points. Miami’s mediocre offense won’t get a lot done against an elite defense, playing in maybe the toughest stadium for any visiting team.

Prediction ATS: Seattle

New York Giants (PK) at Dallas Cowboys

No matter how good Dak Prescott looked in the preseason, he’s still a fourth-round draft pick that’s about to make his first NFL start at quarterback. Eli Manning had two of his best seasons in 2014 and 2015, and the Giants could have one of the NFL’s top offenses in 2016.

Prediction ATS: New York

Detroit Lions (+3.5) at Indianapolis Colts

Andrew Luck and the Colts have made a living off beating up on the NFL’s weakest teams in the last few years, and Detroit falls into that category. Without Calvin Johnson, the Lions are in for a long season, and it might only be a matter of time before Jim Caldwell is out of a job.

Prediction ATS: Indianapolis

New England Patriots (+6) at Arizona Cardinals

Tom Brady might be the greatest quarterback of all time, but Bill Belichick has arguably been more important to the Patriots’ success over the last 15 years. He helped the team win 11 games with Matt Cassel at quarterback, and he’ll keep New England competitive with Jimmy Garoppolo under center. The Cardinals are still a playoff team, but they might not be as good as they were a year ago, giving the Patriots a chance to keep it close in Week 1.

Prediction ATS: New England

Pittsburgh Steelers (-3) at Washington Redskins

Between Washington’s poor defense and Pittsburgh’s explosive offense, the Steelers might put up more points in Week 1 than any other team. Kirk Cousins won’t be as good as he was a year ago, and the Redskins could struggle to start the season.

Prediction ATS: Pittsburgh

Los Angeles Rams (-2.5) at San Francisco 49ers

San Francisco will likely finish at the bottom of the NFC West, but they’ve got a chance to steal a win in Week 1. As bad as Blaine Gabbert is, Case Keenum isn’t much better, and it’s hard to pick the Rams when they’re road favorites while he’s their starting quarterback.

Prediction ATS: San Francisco