The 2021 Southern Illinois 100 presented by Lucas Oil was the 17th stock car race of the 2021 ARCA Menards Series season, and the 35th iteration of the event. The race was held on Sunday, September 5, in Du Quoin, Illinois at the DuQuoin State Fairgrounds Racetrack, a 1 mile (1.6 km) permanent clay oval-shaped track at the DuQuoin State Fair. The race took 104 laps to complete due to an overtime finish. At race's end, Landen Lewis of Rette Jones Racing would dominate the race, leading every lap en route to his first career ARCA Menards Series win. To fill out the podium, Ty Gibbs of Joe Gibbs Racing and Ken Schrader of Fast Track Racing would finish second and third respectively.