Knost, 23, opened the tournament with an 8-under 64 and led after each round at Highland Springs Country Club. He finished 26-under 262 to beat Webb Simpson, who was making his first start on the Nationwide Tour.
Oskar Bergman (65) was third, six shots back, and Josh Broadaway (64) and Brendan Steele (66) tied for fourth, seven back.
Knost earned $108,000 for his second win of the season and jumped from 20th on the money list to second. The top 25 money leaders get their tour cards for 2009.
This is special because I know where it gets me next year, Knost said. This is what we work for, to get to the PGA TOUR.
Knost birdied three of his first six holes Sunday, but he was overtaken for the lead by Simpson, who qualified for the field Monday. Simpson made four birdies in his first five holes and was 6-under after nine holes in the final round.
Knost regained the lead on the par-5 11th after his approach from 205 yards stopped 18 inches from the cup. He tapped in for eagle and the lead.