Knost, who won the U.S. Amateur Public Links and U.S. Amateur last year, picked up his first professional win earlier this season at the Fort Smith Classic.
Jarrod Lyle, a two-time champion this year and the Nationwide Tour's leading money winner, is two strokes back at minus-7.
Peter Tomasulo, who ranks 11th on the money list, is one of 10 players tied for third at 6-under 66 at Highland Springs Country Club.
Knost played the back nine first and opened with a birdie on the 10th. He gave that shot right back with a bogey on the par-5 11th.
He dropped in back-to-back birdies from the 12th, then birdied the 18th to make the turn at minus-3.
Knost birdied the first and second to make it three in a row. He parred the next two, then birdied the fifth to get to 6 under.
'Today, I told myself to be aggressive with the iron shots,' stated Knost. 'I'm a high-percentage player I guess. I make very few mistakes and just play the percentages. For me, I hit my irons well and so I need to be aggressive out here.'
Knost parred six and seven before closing with a pair of birdies to grab the first round lead.
'Obviously, scores on the Nationwide Tour are really low and pars are really not that good,' Knost said.
Lyle opened with birdies on one and two, but he gave a shot back with a bogey on the sixth. He again made consecutive birdies from the eighth to make the turn in three-under.
The Australian eagled the par-5 11th to jump up the leaderboard. Lyle managed to grab second place with birdies on 15 and 17.
'This is the kind of course where you've got to make birdies,' Lyle explained. 'If you're shooting par or even 1 or 2 under, you're backing up. You've got to be aggressive. The toughness of this golf course is where they're tucking these flags.'
Tomasulo was joined in third place by Arjun Atwal, Keith Nolan, Vance Veazey, Camilo Benedetti, Sebastian Fernandez, Josh Broadaway, Webb Simpson, Chad Ginn and Michael Putnam.
Eleven more players, including CBS announcer Bobby Clampett, are tied for 13th at minus-5.