The German, in control throughout at Pinehurst, carded a one-under 69 in his final round to finish at nine-under overall.
Americans Rickie Fowler (72) and Erik Compton (72) were the only others to finish under par ” and a long way back ” but the tournament belonged to Kaymer.
Kaymer, 29, added to the PGA Championship he won in 2010 in the most convincing fashion.
With a 10-foot par putt on the 18th hole, Kaymer became the first German to take out the US Open after a wire-to-wire victory.
He looked up and laughed, perhaps stunned by his dominance and the easiness of what was a stunning win.
Kaymer mixed four birdies with three bogeys in his final round, but he was never seriously challenged.
Compton and Fowler both endured rollercoaster rounds, the latter left to rue a double bogey at the par-four fourth.
Swede Henrik Stenson (73) and Australian Jason Day (68) were tied for fourth with Americans Keegan Bradley (67), Brooks Koepka (71) and Dustin Johnson (73) at one over.
World number one Adam Scott (69) ended up tied for ninth, alongside Jimmy Walker (69) and Brandt Snedeker (73).
English defending champion Justin Rose (72) recovered to be tied for 12th, while Rory McIlroy (73) was tied for 23rd.
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