The 21-year-old former tournament winner played 30 holes on Friday after rainstorms forced a seven hour delay during Thursday's opening round.
She played 12 holes in the morning to complete her first round of eight under and a one-stroke lead at the Blythefield Country Club in Grand Rapids, Michigan.
In the afternoon she rolled in nine birdies and one bogey for back to back 64s which extended her clubhouse lead to three strokes over second place Brittany Altomare, who shot a second round 65.
"I started off really well late last night and I was able to carry it on early this morning," said Henderson, who won this tournament two years ago. "Then I had lunch and came right back and played another 18.
"I just felt really confident today with my ball-striking, which is awesome, and I rolled in a few putts, too."
Henderson, who won the 2016 Women's PGA Championship, finished with a two round total of 16-under 128.
Altomare was alone in second with a 13-under 131, followed by fellow American Jennifer Kupcho, who shot two straight 67s to reach 10-under. The second round was suspended because of darkness with about two dozen players still on the course.
Henderson's opening round included a hole-in-one on the par-three 15th which she aced just before Thursday's round was halted.
It was one of three hole in ones on 15 with the other two coming from Mariajo Uribe on Thursday and Hara Nomura on Friday.
"I'm pretty tired right now, not a lot of sleep last night with the late night, early morning, so I look forward to some rest later tonight," Henderson said. "I think it kind of was a bonus when I had things rolling just to keep it going."
Henderson is hoping a victory this week which would give her a ninth title and sole possession of the all-time Canadian win record. Former Masters winner Mike Weir and George Knudson both have eight PGA Tour titles. Sandra Post also had eight career wins on the LPGA.
Meanwhile, Moriya Jutanugarn hit a second round 67 for a midway total of eight under-par-136 for tied fifth.