Englishman Donald, whose most recent tournament victory came at the 2013 Dunlop Phoenix in Japan, birdied three of his last eight holes to fire a five-under-par 66 at the picturesque Harbour Town course on Hilton Head Island.
Donald racked up six birdies and a lone bogey in cool, blustery conditions to end the day level with South African Branden Grace, a seven-times winner on the European Tour who is still seeking his first PGA Tour title.
Australian world number one Jason Day was also at five under with just one hole to play but got an unfortunate break at the par-four 18th when his second shot ended up in a plugged lie under the lip of a bunker guarding the front left of the green.
After taking an unplayable, Day did well to splash out to six feet and sink the putt for a bogey and an opening 67, finishing level with Americans Matt Kuchar and Tony Finau, and Swede David Lingmerth.
"It was a little bit unlucky but I shouldn't have been in that bunker in the first place," Day, who has won twice in his last three PGA Tour starts, told Golf Channel. "I'm just glad I got a bogey out of it.
"I had played good up until that point so I'm not too disappointed ... not the way I wanted to finish but I played very nicely throughout the whole day to shoot 67."
Donald, who has not triumphed on the PGA Tour since the 2012 Transitions Championship while his world ranking has plummeted to 95th, was delighted to make a good start at a venue where he has been a runner-up on three occasions.
"This year, and even last year, I've been looking for a tournament where I can get in contention and hopefully pick up a win," said the 38-year-old. "It's always nice to come back to familiar places where you've been very successful.
"You feel a little bit more of a comfort level and even though they did a little restoration to this place (on the greens), it's pretty much the same golf course. It was nice to get off to a solid start."
American Bryson DeChambeau, making his professional debut this week after ending his amateur career with a tie for 21st at last week's Masters, opened with a 70.
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