Jeff Burton won the pole against teammate Clint Bowyer. Burton led 7 laps and was briefly challenged by Kasey Kahne. However Burton pulled ahead of Kahne after Kahne led a lap against Burton.
On lap 19, the second caution of the race occurred when Boris Said crashed in turn 3. Said, who nearly pulled off the season's biggest upset and almost won the Pepsi 400 the previous month in July, had gotten some contact with Reed Sorenson. Boris Said climbed out of his demolished #60 No Fear Ford and waved to the fans before riding off in an ambulance. In an interview minutes later, Said said "Guess he was doing his business and I was doing my business and our businesses collided."
Jeff Burton ended up leading the most laps of the race, but pit stop issues resulted in Burton restarting in 20th place and not recovering. With Burton out of contention to win, Jimmie Johnson took the lead and dominated the rest of the event. Kyle Busch challenged Johnson with a few laps left, but Jimmie reclaimed the lead in no time, to win the 2006 Brickyard 400.