The Bills will open their new stadium in Week 2.
The NFL announced Monday that Buffalo will host the Lions on Thursday Night Football on Sept. 17. It will be the first game played at Highmark Stadium.
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Prime Video will broadcast the game as part of its Thursday Night Football package.
The Bills are replacing their longtime home, which opened as Rich Stadium in 1973, with a new $2 billion facility across Abbott Road.
The Bills have won their past four home openers dating to 2022, averaging 38.5 points per game.
The NFL will announce the full schedule on Thursday.