The Tampa Bay Buccaneers will kick off the new NFL season against the Dallas Cowboys on September 9, while Sam Darnold is to be quickly reunited with the New York Jets.
Ahead of the full schedule release later on Wednesday, the Week 1 slate was confirmed with Tom Brady's Bucs the highlight.
After winning the Super Bowl against the Kansas City Chiefs last season, seven-time champion Brady is in the Thursday night game against the Cowboys in Tampa.
The Bucs have brought back the entirety of their title-winning team and face a Dallas outfit aiming to improve on an awful 2020 after signing Dak Prescott to a long-term contract.
Elsewhere, quarterback Darnold will make his Carolina Panthers debut against the Jets team he left this offseason.
In three miserable years in New York, Darnold threw for 45 touchdowns and 39 interceptions across 38 games with a 59.8 completion percentage – the third-worst rate in the league over this period.
The former third overall pick was traded to the Panthers last month for a sixth-round pick this year and a second and fourth-rounders in 2022, with the Jets then using the second selection in 2021 to take Zach Wilson.
Among Wilson's fellow first-round QBs, Mac Jones could potentially make his bow against the man he succeeded at Alabama.
Jones, who is competing for the starting spot on the New England Patriots with Cam Newton, will hope to face Tua Tagovailoa and the Miami Dolphins in a big AFC East matchup.
Trevor Lawrence is likely to go straight into the Jacksonville Jaguars team against the Houston Texans, while Trey Lance will hope to get his chance under center for the San Francisco 49ers at the Detroit Lions and Justin Fields for the Chicago Bears at the Los Angeles Rams in the late Sunday game.
The NFL also confirmed Wilson and Lawrence would be in line for appearances in the London games in October, with the Jets facing the Atlanta Falcons and the Jaguars taking on the Dolphins on consecutive weekends.
Another of the more intriguing Week 1 games sees the Green Bay Packers travel to the New Orleans Saints.
As the Saints begin the post-Drew Brees era, the Packers will hope wantaway MVP Aaron Rodgers is still on the team and able to improve his 3-2 career record as a starter against New Orleans.
The Seattle Seahawks, who have kept hold of Russell Wilson, face the Indianapolis Colts, and Patrick Mahomes' latest title tilt sees the Kansas City Chiefs host the Cleveland Browns.
Mahomes went down with a toe injury and then a concussion in an epic Chiefs win over the Browns in the 2020 postseason, with 35-year-old backup Chad Henne making his playoff debut and having a pick and a sack but completing six of eight passes to complete the job.
In the first Monday Night Football of the season, Lamar Jackson's Baltimore Ravens will go to the Las Vegas Raiders.
Week 1 schedule in full:
Dallas Cowboys at Tampa Bay Buccaneers – Sep 9, 8:20pm ET
Pittsburgh Steelers at Buffalo Bills – Sep 12, 1:00pm ET
New York Jets at Carolina Panthers – Sep 12, 1:00pm ET
Seattle Seahawks at Indianapolis Colts – Sep 12, 1:00pm ET
Los Angeles Chargers at Washington Football Team – Sep 12, 1:00pm ET
San Francisco 49ers at Detroit Lions – Sep 12, 1:00pm ET
Arizona Cardinals at Tennessee Titans – Sep 12, 1:00pm ET
Philadelphia Eagles at Atlanta Falcons – Sep 12, 1:00pm ET
Minnesota Vikings at Cincinnati Bengals – Sep 12, 1:00pm ET
Jacksonville Jaguars at Houston Texans – Sep 12, 1:00pm ET
Cleveland Browns at Kansas City Chiefs – Sep 12, 4:25pm ET
Green Bay Packers at New Orleans Saints – Sep 12, 4:25pm ET
Miami Dolphins at New England Patriots – Sep 12, 4:25pm ET
Denver Broncos at New York Giants – Sep 12, 4:25pm ET
Chicago Bears at Los Angeles Rams – Sep 12, 8:20pm ET
Baltimore Ravens at Las Vegas Raiders – Sep 13, 8:15pm ET