McIlroy on a roll in Ohio
But the Northern Irishman, who won the BMW PGA Championship on Sunday, might have been five strokes clear of the field had he not spoiled his remarkable run over the back nine with a double bogey on the par-four 14th hole.
McIlroy put the distress caused by his publicised break-up with Danish tennis player Caroline Wozniacki to one side last weekend to clinch a surprise victory at Wentworth and that winning momentum followed him to Muirfield Village.
Birdies on the second, fourth and seventh holes followed a run of two birdies and an eagle over the turn before he picked up a sixth shot on 13.
At eight under he was two strokes clear of the three men who had already carded 66, but briefly joined Casey and the American duo in a tie for the lead after finding the rear bunker on 14 and needing a total of six shots to hole out.
McIlroy remedied that situation immediately by draining a 15-foot putt to claim his second eagle of the day before adding one final birdie on the 16th.
Casey, currently 97th in the official world rankings, started with a bogey but reached the turn four under having drained an eagle on the par-five seventh.
He mixed three more birdies with a bogey between 14 and 17 while Kirk's seven birdies and a bogey kept him in sight of the lead.
Reigning Masters champion Watson might well have finished on eight under but dropped shots on 16 and 17.
Most notable in the group of Americans was Bradley, who registered a bogey-free five-under 67 - recording only 27 putts - after making the switch from his favoured anchored putter to a non-anchored flatstick.
The Australian's run of five birdies and a bogey across seven holes on the front nine was sullied by a double bogey on the ninth and, like Spieth, he lies six strokes off the early pace set by McIlroy.