American Reed birdied his final two holes for a bogey-free, six-under-par 64 on a calm, mild morning at Sedgefield Country Club.
"To be able to putt on really fast greens like this, it's a treat," Reed told reporters after posting an 11-under 129 halfway total.
Fellow American Jordan Spieth carded a 66 to sit a further two strokes back at nine under, two better than South Korean Charlie Wi (65) and Englishman Ross Fisher (69).
Defending champion Sergio Garcia, among a large group in joint third place overnight, shot a respectable 70 to slip six strokes off the pace.
Reed, 23, made his first cut on the PGA Tour here two years ago, but he has his sights set far higher this week after finishing in the top 10 in his past two events.
"We've been working extremely hard trying to fine-tune everything, and lately with how I've been hitting the ball and how I've been putting, it just seems to all be clicking," he said.
"I just need to put four rounds together and hopefully that's this week."
If Reed wins, he will happily give his caddie 100 percent of his prize money, because his wife Justine carries his bag.
"She knows just as much about the golf swing, why I hit it left or right or anything like that, so if I ever get out of whack she can fix me immediately," Reed said.
Garcia, meanwhile, lamented a cold putter, not for the first time in his career, after missing five putts from inside seven feet.
"I would have loved to shoot at least a couple under (par) today. I feel I played well enough to do it but I didn't," the Spaniard said.
"I wasn't able to hole it as well as yesterday from four, five, six feet."
American journeyman Chris Stroud, co-leader overnight with Fisher after opening with a 64, was among the day's late starters.