Knost completed three rounds at 16-under 200 and had a one-shot advantage on three players.
The Nationwide Tour rookie will be looking to become only the second two-time winner this season after he picked up his first career victory earlier this season at the Fort Smith Classic in May.
Knost also won both the U.S. Amateur Public Links and U.S. Amateur last year.
James Love, Webb Simpson and Vance Veazey all posted rounds of 5-under 67 on Saturday to share second place behind Knost at 15-under 201. Five players were another shot further back at 14-under 202.
Overall, there were 27 players within five shots of Knost's lead after three rounds of good scoring at Highland Springs Country Club.
Each day the leaderboard has bunched up behind Knost, and each day he has managed to come out on top.
When he woke up on Saturday, Knost saw that some one was seven-under through 11 holes and sitting in second place. Stuff like that can happen, he figured, and it meant that he had to play more aggressively.
'I know I can't go out and play to the middle of the greens and stuff,' Knost said. 'I made plenty of birdies today, I just made too many bogeys.'
His 69 on Saturday, which included six birdies and three bogeys, marked his worst score of the week by two shots. He opened with a 64 on Thursday to take the first-round lead, then protected it with a 67 on Friday.
'It was a pretty frustrating day,' said Knost.
Although he lost his exemption to this week's British Open -- as well as the Masters and U.S. Open -- when he turned pro following his amateur wins last summer, Knost is making the best of that decision.
Ranked 20th on the money list entering this week, he is in good position for a top-25 finish at the end of the season, which would garner the talented 23- year-old rookie a PGA TOUR card for next year.
A win on Sunday could carry him to No. 3 on the money list.
'I know there's a lot on the line tomorrow. I've just got to take it one shot at a time and go out and be aggressive,' said Knost.