Busch, whose first victory of the season came on the same 1.5-mile oval in April, matched Sam Ard's season record set in 1983. He held off a charging Carl Edwards in the final laps of the O'Reilly Challenge.
The strong run by Edwards, combined with Clint Bowyer's sixth-place finish, moved Edwards within 91 points of the series leader with two races remaining.
Although Busch has had a disappointing run in the Chase for the Sprint Cup and is out of contention for the title despite dominating the regular season, he has a total of 21 victories this season, including eight in Cup and three in trucks.
But this one was special as the 23-year-old Busch dedicated the latest win to South Carolinian Ard, a two-time Nationwide --then called the Busch Series -- champion suffering from Alzheimer's disease and in tough straits financially.
"Sam Ard was one of the pioneers of the sport and this really means a lot to me," Busch said after his now-traditional victory bows to the crowd. "I got to thinking about it and I decided I'm going give him $100,000 to try to help him out."
Edwards, who won the Nationwide title a year ago, is second in both this series and Cup, where he will try to cut into Jimmie Johnson's 183-point margin in Sunday's Dickies 500.
Edwards gave up some track position Saturday, falling from second to fifth when he took four fresh tires during a late pit stop, while Busch and Mark Martin, who finished third, took two. But Edwards quickly moved forward, taking second place from Martin on lap 196 and getting within three car lengths of the leader on the final lap.
"Man, I needed about two more laps," said Edwards, who drove from fifth to second after the final restart with seven laps to go. "We got 25 points on (Bowyer) today and now 91 points is completely doable, so I'm happy about that.
"We both had good cars today, but we got him with that late call (for four tires) and a little bit of traffic at the end."
Bowyer began the day 116 points ahead of Edwards and appeared to have one of the best cars on the track until he faded late in the race.
"We just got real tight at the end. We'll be all right," Bowyer said. "All-in-all, it was a good day."
But this day belonged to Busch, who led 174 of the 200 laps. The youngster, who has raced in only 28 of the 33 Nationwide events this season and is not a factor in the points race, also led 126 of 200 laps in the April win.
Saturday's victory was the 21st career win for Busch in Nationwide and the 19th win in the series this season for Joe Gibbs Racing.
"The year's not over, yet," Busch said. "I don't even know all the numbers, to tell the truth. It's just phenomenal the way this year's gone. But a lot of the success belongs to Joe Gibbs Racing and what they've done this year."
Eighteen-year-old Joey Logano, another JGR driver, turned in another solid performance, finishing fourth, with David Ragan fifth.
Kevin Harvick, who had won the past three fall Nationwide races here, ran in the top 10 most of the day, but wound up 29th after breaking an axle as he left the pits following a stop late in the race.
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