Reed, who has made a name for himself as a US Ryder Cup stalwart, was scheduled to tee off at 2:30 (1930 SA time) alongside Australian Marc Leishman, who was two strokes back and also in pursuit of a first major title.
Until this week, Reed had never broken 70 in 12 career rounds at the Masters.
However, his confidence was soaring after rounds of 69 and 66 left him at 9-under 135.
"I feel like I've done all the work," Reed said. "I feel like I know where I need to leave the golf ball ... and it's now just going out here and executing the game plan and staying disciplined enough to actually stick to that game plan.
"I've been doing that the first two days, and it's allowing me to kind of attack this golf course and not make a lot of mistakes."
If he does make a mis-step, there are plenty of big-name players poised to pounce.
Eight reigning and former major champions are within seven shots of the lead, starting with 2016 British Open champion Henrik Stenson, who was alone in third on 139.
Northern Ireland's Rory McIlroy, who can complete a rare career Grand Slam by slipping on his first green jacket on Sunday, was five strokes back, tied for fourth with reigning British Open champion Jordan Spieth, whose 2015 Masters triumph was sandwiched between two runner-up finishes.
This is the fourth time the 28-year-old McIlroy has arrived at Augusta National with a chance to complete his collection of major trophies.
McIlroy has come close before in the Masters, taking a four-shot lead into the final round in 2011 but carding an agonizing final-round 80.
He went on from that experience to win the 2011 US Open, and after being hindered by injury in 2017 he's back in the top 10 in the world after a victory at Bay Hill last month and sounded a confident note after a second-round 71 that he thought could have been even better.
Spieth, who led after a first-round 66, came back to the pack on a difficult, windy Friday, when he dropped three shots in the first two holes but rebounded to card a 74.
"So what's a couple of holes on a Friday start mean?" he said of his double bogey-bogey start on Friday. "It really doesn't mean much to me. I'm still in a great position."
McIlroy and Spieth were one stroke in front of another pair of major winners – world number one Dustin Johnson and world number two Justin Thomas, who just happen to be tussling for the top spot in the rankings this week as well.
All of the contenders can expect to face rain, and possibly thunderstorm delays, on Saturday afternoon.
Spieth said bring it on.
"Obviously, it becomes a technical golf course when the conditions get tougher and you're presented with kind of tough breaks," he said. "And I think that's an advantage for me. I feel like I tactically play this course very well."
The rain had already started by the time 14-time major champion Tiger Woods arrived on the driving range to warm up for his 10:40 a.m. (1440 GMT) start.
Woods, back at the Masters for the first time in three years, didn't produce the magic his legion of fans had hoped for over the first two rounds.
But the 42-year-old, who didn't know six months ago if he'd be able to resume his golf career, was delighted to give himself two more rounds at Augusta.
And in typical Tiger fashion, he wasn't throwing in the towel even though he went into the day 13 shots off the lead.
"Even though I'm a lot behind, if I play a special weekend – shoot two rounds in the mid-60s – you never know," he said.