The German has been in control throughout at Pinehurst and is in a commanding lead despite a two-over 72 as he sits at eight under overall.
Back-to-back 65s had the 2010 PGA Championship on track and while he was unable to reproduce it, he should still have enough to go on and win a second major.
American duo Rickie Fowler (67) and Erik Compton (67) surged into a share of second as they sit at four under.
Swede Henrik Stenson (70) and American Dustin Johnson (70) are a further shot back in a tie for fourth, while Brandt Snedeker (72) is the only other player under par.
Kaymer had holed just one bogey in his opening two rounds, but he quickly added to that tally on Saturday.
He bogeyed three of his first six holes, but an eagle at the 530-yard par-five fifth meant his round was under control.
Kaymer bogeyed the 13th and 15th holes and birdied the 18th to be perfectly placed heading into Sunday.
Fowler mixed five birdies with two bogeys, while Compton endured a rollercoaster round that included an eagle at the fifth.
American trio Matt Kuchar (71), Brooks Koepka (72) and Kevin Na (73) are tied for seventh at even par.
English defending champion Justin Rose (70) continued his recovery from an opening-round 72 to be equal 10th.
Zimbabwean Brendon de Jonge (73) is alongside Rose, as are Americans Jordan Spieth (72) and Chris Kirk (72).
World number one Adam Scott (73) is too far back at three over, joined by Northern Irishman Rory McIlroy (74) and Australian countryman Jason Day (72).
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