Wittenberg, the runner-up at the 2003 U.S. Amateur Championship, finished 54 holes at 15-under 199 and is one stroke ahead at The Georgian Bay Club.
Bubba Dickerson, the winner of the 2001 U.S. Amateur, shot a 4-under 67 and is tied for second place with U.S. Open first-round co-leader Justin Hicks (67) and Sebastian Fernandez (68). The trio came in at 14-under 200.
Wittenberg and his closest pursuers all are winless on the Nationwide Tour.
'I'm looking forward to tomorrow,' said Wittenberg, who is 13th on the Nationwide Tour money list. 'My goal is to get my PGA TOUR card. I'm just fortunate enough to give myself the opportunity to get it done.'
Wittenberg got off to a shaky start with a bogey on the first hole, but atoned for the error with a birdie at the second hole. He collected back-to-back birdies at seven and eight to get to 13-under for the championship.
He added birdies at 11 and 14 to get to minus-15, then held on with pars when others faltered down the stretch.
'Luckily today I was able to play from the fairway,' said Wittenberg. 'It was tough out there. The ground was so wet. But you still have to make birdies when the conditions are not good. You have to find a way to do it.'
Overnight co-leader Kyle McCarthy only managed a one-under 70 and is tied for fifth place with Matt Every (67), Kyle Reifers (67) and Michael Putnam (68) at 13-under 201.
David Mathis (66), Gibby Gilbert III (70) and Chris Tidland (70) share ninth at minus-12.
D.A. Points, who shared first with McCarthy on Friday, struggled to a 1-over 72 and fell into a tie for 12th at 11-under-par 203.