Seeking a second major title after clinching his first in the 2010 PGA Championship, Kaymer produced sizzling form on a hot and sunny afternoon as he fired a five-under-par 65 on Pinehurst's fabled No. 2 Course.
Out in one-under 34, the 29-year-old German stormed home with birdies at the 10th, 14th, 16th and 17th to take control of the second of the season's four majors on a layout that had been softened overnight but became increasingly firm on Thursday.
"I would have never expected myself to shoot such a low round at Pinehurst because of the conditions, but it's a very, very good round of golf," Kaymer told reporters after shooting the lowest ever score at the venue in a US Open.
"I just played really well today. I didn't make many mistakes, I hit a lot of fairways, I hit a lot of greens. It is a good start, but that's it. There's nothing more than that.
"Five under par is exceptional. But it is not normal, so no one really should expect me to shoot another five under the next three rounds," said Kaymer, who gained a major confidence boost from his victory at the elite Players Championship last month.
Former champion Graeme McDowell, without playing at his best, delivered a consummate display of course management to card a 68 and ended the round level with Americans Kevin Na and Fran Quinn and burly Zimbabwean Brendon de Jonge.
McDowell, who claimed his only major title in the 2010 US Open at Pebble Beach, was delighted with his start.
"I played it very conservatively," the Northern Irishman said after carefully negotiating Pinehurst's No. 2 Course where danger lurked on virtually every hole because of the challenging turtle-back greens.
"I positioned the ball great off the tee. I drove it really well all day. I generally kept the ball exactly where I wanted to going into the flags, short of a lot of the greens on the correct side of most of the flags.
"It wasn't my best ball-striking display this morning, but you don't have to strike it amazing around here, you just have to position the ball correctly at all times," said the 34-year-old from Portrush.
BACK-TO-BACK WINS
Defending champion Justin Rose of England, aiming to become the event's first back-to-back winner in 25 years, launched his title defence with a 72.
"I hit every tee shot just as I wanted to," Rose said after mixing three birdies with five bogeys and totalling 30 putts. "I'm swinging it much better than I have been and I played the par-threes really well.
"Just my short game was very poor. I need to work on that."
Rose played in a high-profile trio that attracted the biggest galleries of the day and included British Open champion Phil Mickelson, who has suffered more US Open heartache than any other player.
The American left-hander, who has been a runner-up in his national championship a record six times, ground out an even-par 70 in the opening round to finish five strokes off the pace.
"I drove it great," said British Open champion Mickelson, who would become the sixth player to complete a career grand slam of the four majors with victory this week. "Every time I hit driver, I hit the fairway.
"I putted OK but didn't make the ones you need to make, the 15, 20-footers, you need to have a good round."
Northern Irish world number six Rory McIlroy, the 2011 US Open champion at Congressional where he blew away the field with a stunning eight-stroke victory, opened with a 71.
World number one Adam Scott, grouped with fellow Masters champions Bubba Watson and Charl Schwartzel in one of the most eye-catching trios of the day, struggled to a 73 that included four bogeys and a lone birdie.
"I'm a little disappointed," said Scott, who is bidding for his second major title after clinching his first at last year's Masters.
"I played a little better than what I ended up shooting. Around this kind of golf course, I just put it down to my short game not being spot on today."
Reigning Masters champion Watson fared even worse on the way to a 76 while South African Schwartzel, who claimed his green jacket at Augusta National in 2011, opened with a 70.
