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Adrian Peterson has the most rushing yards in a game, with 296 yards versus the San Diego Chargers on November 4, 2007.

what is the most rushing yards in a game
Interpreted as:
What is the most rushing yards by a player in a regular-season game?
11/4/2007Peterson9/14/2003Lewis12/20/2009Harrison10/22/2000Dillon11/20/1977Payton11/25/1976Simpson11/11/2001Alexander1/3/2010Charles11/24/2024Barkley1/3/2021Taylor10/23/2011Murray11/4/2012Martin12/3/2000Anderson1/3/2021Henry9/16/1973Simpson12/5/1971Ellison12/4/1997Dillon12/28/2003Tomlinson12/8/1963Gilchrist12/6/2018Henry11/13/1994Sanders10/31/1993Smith296295286278275273266259255253253251251250250247246243243238237237
Results may be incomplete. StatMuse has complete game-level data for rushing yards going back to the 1960 season.

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