Bernhard Langer and Fred Funk opened with 67s on the Ocean Hammock Golf Club course, and David Edwards and Gene E. Jones had 68s in the Champions Tour's deepest field this season.
Former Masters champion Craig Stadler was among those at 69 and defending champion Keith Fergus and Tom Watson were at 70. Ian Woosnam struggled in his Champions Tour debut, making two double bogeys in a 78.
Nielsen played the PGA Tour from 1978-83. His best finish was a tie for fifth in the 1979 Quad Cities Open. He worked as a club pro in New York state and qualified for the Champions Tour in 2003. Nielsen has won once, the 2007 Commerce Bank Championship.
He rallied from a double bogey at the par-3 12th hole, his third hole of the day, and began a torrid run up the leaderboard with an 8-foot birdie putt at the 18th. Nielsen then birdied Nos. 1, 2, 4, 6 and 7 to pull ahead of Langer and Funk.
"I'm feeling more comfortable out here," Nielsen said. "That's half the battle. It sounds simple, but it's a lot tougher than it sounds."
Langer hit the shot of the day, a 6-iron from 188 yards that he holed for an eagle-2 at the 13th. He also birdied three of the four par 5s. He made two clutch chips on his last two holes.
"The long game wasn't quite as good as I wanted it, but the putter was good and the short game was good," Langer said. "I've had plenty of days where I played well and didn't get much out of it, so I would rather play not so well and score well."
Funk birdied the 16th to tie Nielsen for the lead, but dropped a shot with his only bogey of the day on the next hole. The 67 matched his best opening round of the season in five starts on the Champions Tour and four on the PGA Tour.
"I played great," Funk said. "The greens were real firm and real fast and it was a good test out there."