The first NFL game of the regular season typically takes place on the Thursday following Labor Day in early September. For the 2025 NFL season, the first game is scheduled for Thursday, September 4, 2025. The Dallas Cowboys will face off against the Philadelphia Eagles in Philadelphia to kick off the season. This tradition of starting the season with the defending Super Bowl champion hosting their first game has been followed since 2004 with some exceptions. The Eagles are the reigning champions coming into the 2025 season.

Historically, the NFL kickoff game was introduced in 2002 as a season opener event. Also, the very first NFL game ever played was hosted by the Dayton Triangles on October 3, 1920, at Triangle Park against the Columbus Panhandles, marking the start of the league now known as the NFL.

In summary:

• The NFL regular season usually starts the Thursday after Labor Day.
• The 2025 NFL season's first game is on September 4, 2025, between the Dallas Cowboys and Philadelphia Eagles.
• The league's first-ever game took place in 1920 between Dayton Triangles and Columbus Panhandles.

This answers when the first NFL game of the season and historically the very first NFL game were played.