The 2021 NFL season begins with Tampa Bay raising its Super Bowl banner in front of a Dallas team that welcomes Dak Prescott back from injury.
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| Detroit Lions vs Los Angeles Chargers | |
| Type: Point Spread - Status: OPEN | |
| Detroit Lions | -105 |
| Los Angeles Chargers | -115 |
| Philadelphia Eagles vs Dallas Cowboys | |
| Type: Total - Status: OPEN | |
| Under | -105 |
| Over | -115 |
| Philadelphia Eagles vs Chicago Bears | |
| Type: Moneyline - Status: OPEN | |
| Philadelphia Eagles | -320 |
| Chicago Bears | +260 |
| Washington Commanders vs Philadelphia Eagles | |
| Type: Moneyline - Status: OPEN | |
| Washington Commanders | +100 |
| Philadelphia Eagles | -120 |
| Chicago Bears vs Green Bay Packers | |
| Type: Moneyline - Status: OPEN | |
| Chicago Bears | -105 |
| Green Bay Packers | -115 |
| Kansas City Chiefs vs Denver Broncos | |
| Type: Moneyline - Status: OPEN | |
| Kansas City Chiefs | -200 |
| Denver Broncos | +170 |
| AFC Conference vs NFC Conference | |
| Type: Moneyline - Status: OPEN | |
| NFC Conference | -105 |
| AFC Conference | -115 |