The Joe Gibbs Racing driver beat his team-mate Joey Logano in a close finish at the half-mile venue, breaking Mark Martin's record of wins in the second-tier series, which the veteran held since 1997.
Busch's maiden Nationwide win came in 2004 at Richmond at the age of 19 while driving for Hendrick Motorsports. He has now competed in 219 events in the series, meaning he has won 22 per cent of the races he has entered.
In 2008, he tied the record for victories in a single season with 10, matching two-time champion Sam Ard, while in 2010, he broke that record by winning 13 times. He was also the 2009 champion.
"There's an awful lot of accomplishments and it's hard to pinpoint exactly where they fall but certainly tonight's a pretty big one," said Busch. "Just being able to race that hard and race against a team-mate like that, knowing that he had just as good of stuff as I did.
"Certainly, it was great to have Mark [Martin] with us in victory lane in Loudon and take some photos with him for tying him. Tonight was our night.
"Being able to beat him and get atop the all-time win list in the Nationwide Series was special for us as a team and for me as a driver and [wife] Samantha as well.
"This is cool and hopefully we can come back and perform again tomorrow night and do the same thing."
The 26-year-old American is currently the Sprint Cup series leader, and potentially tops the Chase standings thanks to his four wins thus far this season. He is the only driver to have already locked himself in the championship play-off with his victory at Michigan last week.
