Visit Betway’s NFL picks page for picks and predictions throughout the season.

Green Bay Packers (-3.5) at New Orleans Saints -110

While this game is labeled as the Packers visiting the Saints, Hurricane Ida has had something to say about it. The games has been moved to Jacksonville, so the home-field advantage for the Saints gets wiped away. 

The Saints lack the firepower to keep up with last season’s highest-scoring offense. Michael Thomas is out injured, making Alvin Kamara their only real threat.

New Orleans also recently traded for a competent second cornerback in Bradley Roby, but he will not play Week 1 due to a suspension.

Aaron Rodgers and the Packers will continue to lead an efficient offense, beating the new-look Saints. 

Seattle Seahawks (-2.5) at Indianapolis Colts -115

The Colts offense should not inspire any confidence. The left tackle situation is a complete mess until Eric Fisher returns from injury, which seems 50/50 for this week.

T.Y. Hilton is out, so Michael Pittman Jr. becomes the WR1, with Parris Campbell the second-best option. They simply don’t have enough to beat the Seahawks and Russell Wilson.

The Colts also have the tendency to start the season slowly. In fact, they haven’t won a Week 1 game since 2013.

San Francisco 49ers (-7.5) at Detroit Lions -110

This looks to be the most lopsided matchup of Week 1, and the NFL betting odds reflect this.

The 49ers are a Super Bowl contender. In fact, Betway has their Super Bowl odds at +1400, which is the fifth-best. The Lions, on the other hand, have their win total set at 4.5, and the under looks inviting. 

It’s no secret that the injury bug bit the 49ers more than any other team last season, but they are now back healthy. The last time they were this healthy, they were a Super Bowl team.

San Francisco has a great defense, a talented receiving corps and a strong running game. As for the Lions, their top wide receiver is Tyrell Williams, and their quarterback is Jared Goff, who the 49ers know very well since he played in their division his entire career. 

This game may not be close for long. 

Pittsburgh Steelers (+6.5) at Buffalo Bills -110

While this game will be played in front of a rowdy Buffalo crowd, the line is disrespectful to the Steelers. Yes, the Bills are a Super Bowl contender, but we shouldn’t pretend the Steelers aren’t good. In fact, they were 11-0 last season before injuries hit their defense.

Healthy again, this Steelers defense is one of the strongest units in the entire NFL. Offensively, Ben Roethlisberger looks to be in his best shape in some time. Their biggest weakness is their offensive line, but the Buffalo front seven is not intimidating. 

While the Bills are a great team and could very well win this game, Pittsburgh isn’t going to roll over. This game will be closer than the books think.

Cleveland Browns at Kansas City Chiefs (-5.5) -115

After getting embarrassed in the Super Bowl, the Chiefs reloaded. They fully rebuilt their offensive line, which looks ready to beat up on defenses all season long. For the first time since 2019, Kansas City looks motivated, which is a scary thing. 

They seemed disinterested at times in 2020, despite going 14-2. Arrowhead Stadium will be full and the crowd’s energy will be injected into this Chiefs team.

While the Browns improved their defense quite a bit this offseason, they still do not have enough to stop this Chiefs offense.

Tyreek Hill has unguardable speed, while Travis Kelce is still too large for safeties and too quick for linebackers. The Cleveland offense will need to play their best game, which is a lot to ask for a Week 1 game in a hostile environment.