Jeff Quinney, the 2000 U.S. Amateur champion, is also 5-under par, but has one hole left to finish. Eighteen players still need to finish their first rounds as play was halted due to darkness on The Course at Wente Vineyards.
The first round will resume at 10:00 a.m. (ET). Round two will start as scheduled at 9:50 a.m.
Craig Bowden and Gabriel Hjertstedt share third place at 3-under-par 69. Ricky Barnes, the 2002 U.S. Amateur winner, is one stroke further back at minus-2. He stands alongside Jason Buha, Hunter Haas, Tom Johnson and John Merrick.
Isenhour played the back nine first on Thursday. He picked up his first birdie on the par-5 12th. Three holes later, Isenhour dropped in his second birdie effort on the par-5 15th.
The three-time winner on the Nationwide Tour parred his next three holes to turn at minus-2. On the par-4 first, Isenhour tripped to a three-putt bogey. He came right back with a birdie on the second to get back to 2 under.
Isenhour sank back-to-back birdies from the fifth to climb to 4 under. The 37-year-old closed with a birdie on the ninth to get to 5 under.
'I'm a little bit surprised at 5 under because you expect to miss one or two fairways,' said Isenhour. 'This golf course is very difficult with the rough the way it is right now. I've played in two U.S. Opens at Southern Hills and Shinnecock and those courses didn't have the kind of rough we have here.'
Quinney, who was a playoff loser on the Canadian Tour last week, opened with eight straight pars. He then birdied each of his next two holes.
The 2004 Oregon Classic champion parred 11 and 12 before a birdie on the 13th got him within two of the lead. Quinney made it two straight with a birdie on 14 and grabbed a share of the lead as he birdied the 15th. He parred his next two holes before play was halted for the night.
'If you hit it in the rough out here you have no chance,' Quinney said. 'I gave myself a lot of chances. This might be one of the ball-striking rounds I've ever had.'
Former PGA Tour players Joel Kribel and Blaine McCallister both shot 1-under-par 71 and share 10th place. They stand alongside Chad Collins, Ken Duke, Christopher Baryla, Tommy Tolles and Jim McGovern. Matt Bettencourt and Craig Lile both are at minus-1 with two holes left to complete.