Of course, the first matchup will be the most intriguing game. Everyone wants to know how Robert Griffin III's knee holds up, and fans are curious to see how Chip Kelly's offense works in the NFL.
However, there are two games on the schedule. Each of the four quarterbacks have been to the Pro Bowl in their career. Both games feature a playoff team from a season ago, so there will be plenty on the line in each game.
Here are the matchups for Monday Night Football followed by predictions for the two games. Lines are courtesy of Bovada at 11 a.m. on Sept. 8.
Philadelphia Eagles at Washington Redskins
Griffin will be making his first start since suffering the second serious knee injury of his career, and fans are curious to see how he plays.
Washington swept the Eagles last season and blew them out at home. The 23-year-old averaged 199 passing yards and 44 rushing yards with three touchdowns.
As a rookie, he led an offense that ranked fourth in the NFL in points per game. Philadelphia tied for 29th by allowing 27.8 points per game.
With Griffin and Alfred Morris having great rookie seasons, Washington led the NFL in rushing. It averaged 169.3 rushing yards, and the Eagles had a top-10 pass defense. Running the football will lead Washington to a victory, but Griffin will also be expected to throw the ball to keep the Eagles from packing the box.
Kelly is going to want to run an uptempo offense in Philadelphia. Michael Vick, LeSean McCoy and DeSean Jackson will be great fits in the coach's system. The defense is going to have to step up in order for the Eagles to contend though.
Unfortunately for the Eagles, this game is in Washington. It will be an emotional night as the defending NFC East champions get their quarterback back on the field.
Predicted winner: Washington Redskins
Houston Texans at San Diego Chargers
This looks like a big mismatch.
The Houston Texans have won playoff games in back-to-back seasons, and the San Diego Chargers couldn't finish .500 in the AFC West.
At 7-9, the Chargers were able to finish in second place in their division last season, but they lost seven out of eight games in the middle of the season and won only three home games all year.
Houston is one of the most balanced teams in the league. It is extremely balanced on offense and has stars on defense.
Arian Foster ran for 1,424 yards and 15 touchdowns, which led the league. He added two receiving touchdowns. Andre Johnson is still one of the best receivers in the league, and Owen Daniels is a solid tight end. With Matt Schaub at quarterback, the Texans should make another trip to the playoffs this season.
NFL Defensive Player of the Year J.J. Watt will be looking to follow up a great 2012 season, and Johnathan Joseph leads the secondary.
San Diego will be without Danario Alexander this season, so Keenan Allen and the other receivers will have to step up. Philip Rivers has a strong arm, but he needs playmakers to help him.
This game could get out of hand if San Diego's receivers don't show up.
Predicted winner: Houston Texans
*All stats are courtesy of NFL.com