The NASCAR star was dominant across the finale, leading all of the 50 laps to claim his second straight crown and third in total.
He has now led the last 100 A-Main laps at the Nationals off the back of his lights-to-flag win last year.
Larson started from the pole and made a swift start to the first 25-lap sprint to the halfway break.
His lead was quickly out to three seconds, until Carson Macedo put in a charge approaching the break and closed onto the back of Larson.
He couldn’t get through, though, Larson and Macedo finishing in that order with an improving Giovanni Scelzi in third.
After the break Scelzi made more progress, charging past Macedpo and then closing onto the back of Larson, who opted not to take on new tyres for the second 25.
It was the same story as the first half, though, with Scelzi unable to find a way past, even when Larson was slowed in traffic.
In the end Larson was able to stabilise the gap and effectively cruise to victory.
“It doesn’t get any bigger than the Knoxville Nationals so it feels great to lead back-to-back 50 lappers, because there’s the best Sprintcar drivers in the world lined up behind me,” said Larson.
“They don’t make it easy. It was a tricky race, even if at times, it doesn’t look like it, but those lappers were just fast enough around the bottom and I felt like I was slowing myself down.
“We’ve been really bad this year, until the last couple of weeks. It’s been a very disappointing year from our standards and for [the team] to never give up, for myself to never give up either, is tough to do. All of this goes to them for continuing to push and push and get better and better.”
As for the decision to not change tyres at the break, Larson said: “The tyres looked brand new, so what’s there point of changing? I feel like there’s been some inconsistencies this year, so we were able to lead the first 25, why put on a new set and maybe trick yourself?
“I felt better in the second half. We still may some adjustments to the race car and that really helped.”
Corey Day was the hard charger, coming from the sixth row to finish third.
Macedo dropped back to fourth ahead of Anthony Macri, Brian Brown, Tyler Courtney and Aussie Scott Bogucki.