The very first-ever NFL game was played on October 3, 1920, when the Dayton Triangles hosted the Columbus Panhandles at Triangle Park, Dayton, Ohio, with the Triangles winning 14-0.

If the question is about the first game of the upcoming or typical NFL season, the NFL Kickoff Game is traditionally the first game of the regular season and is usually scheduled for the Thursday following Labor Day in early September (between September 4 to 10).

Specifically, for the 2025 NFL season, the first game is scheduled for Thursday, September 4, 2025, with the reigning Super Bowl champion Philadelphia Eagles hosting the Dallas Cowboys.