The German led by five shots overnight despite shooting a two-over-par 72 in his penultimate round at Pinehurst on Saturday.
Kaymer, who is gunning for a second major title after winning the US PGA Championship in 2010, has led after each round following superb back-to-back 65s on the first two days.
He parred the first two holes on day four, and playing partner Rickie Fowler and Erik Compton did likewise to remain five behind on three under.
World number two Henrik Stenson and Dustin Johnson were a shot further back, while an eagle for defending champion Justin Rose at the fifth left him seven off the pace.
Zach Johnson has failed to trouble the leaders this weekend, but the 2007 Masters champion had a moment to savour with a hole-in-one at the 172-yard par-three ninth.
The American celebrated in exuberant fashion by rushing over to the crowd and high-fiving a number of delighted spectators.
Several players have shown that there are low scores to be carded in the final round. Louis Oosthuizen and Jim Furyk both went round in 67, while American Daniel Berger fared even better with a fine 66.
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