Vaughan moved in front at yet another major tournament with a 6-under 64 at the Fox Chapel Golf Club.
Greg Norman, making his first Champions Tour appearance in three years, was among those at 67.
Vaughan's lone victory since turning 50 in 2006 came at the 2008 Senior British Open, where he defeated John Cook in a playoff.
He birdied four holes in a six-hole stretch Thursday beginning at the par-3 third.
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