The 2021 Cook Out Southern 500, the 58th running of the event, was a NASCAR Cup Series race held on September 5, 2021 at Darlington Raceway in Darlington, South Carolina. Contested over 367 laps on the 1.366-mile (2.198 km) egg-shaped oval, it was the 27th race of the 2021 NASCAR Cup Series season, first race of the Playoffs, and the first race of the Round of 16. Denny Hamlin took his first victory of the season and clinched a spot in the round of 12.