'I have a lot more control over my golf ball and my misses are more predictable,' said Isenhour, who pocketed $99,000 for the win. 'You're only as good as your misses.'
Kevin Gessino-Kraft (68), tour rookie Parker McLachlin (69) and overnight co- leader Brenden Pappas (72) shared second place at 8-under-par 272.
Jason Allred shot a 4-under 66 on Sunday and finished alone in fifth place at minus-seven.
Isenhour and Pappas were tied at the start of the final round, but Pappas bogeyed one. That would be all Isenhour needed to secure the win, but three consecutive birdies from the third put the tournament firmly in his control.
'I got off to such a great start,' acknowledged Isenhour, who could have made it worse for the field, but missed a 6-foot birdie putt at the second. 'That was huge.'
Isenhour held on to a large margin despite bogeys at 10 and 11, including a three-putt from 35 feet at the 10th. Pappas fell down the leaderboard with a triple bogey at 11 and no other player staged a rally, so Isenhour cruised.
He parred his final seven holes to hoist the trophy at the season opener.
'I didn't look at a leaderboard all day, but I knew somebody was going to have to play well to catch me,' admitted Isenhour. 'Brendan told me walking down the next fairway that 14 pretty much sealed the deal. I just gutted it up and got it done coming in.'
This win for Isenhour validates an offseason spent on working on his swing. In the final round of last year's PGA Tour Q School, he fell apart on the back nine and never earned his card.
Sunday was a different story.
'I'm surprised that the changes are so far along this quickly and happy that they held up for four days,' said Isenhour. 'This win is so much sweeter because of all the work we did to get to this level.'
Travis Perkins, Mario Tiziani, David Hearn, Scott Petersen and Kyle Thompson all posted matching rounds of even-par 70 on Sunday. They tied for sixth place at minus-5.