The Northern Irishman, who recovered from seven shots behind Thomas Bjorn to win the PGA Championship last Sunday, stormed to a nine under par round of 63, which included two eagles on the back nine.
His closest challengers are Englishman Paul Casey, who shot six under par together with American Chris Kirk and Masters champion Bubba Watson, who birdied his final three holes.
World No1 Adam Scott is six shots behind McIlroy on three under par. England’s Justin Rose, who defends his US Open title next month at Pinehurst in a field that will be missing the injured Tiger Woods, shot one over par.
-6: Casey, Kirk, Watson
-5: Bradley, Thompson, Holmes
-4: Mahan, Moore, Leonard