Fowler, the 2010 PGA Tour Rookie of the Year, started the day in a five-way tie for the lead in a group that included McIlroy and defending champion YE Yang, before moving to a 13-under 200 total for the tournament.
Yang, playing in front of his home crowd, was in second after a 67, two strokes ahead of fellow South Korean Kim Meen-whee, who had a 66.
McIlroy struggled around the course to post a 73, leaving the U.S. Open champion 10 shots off the pace. A nightmare run of four bogeys and one double bogey between the ninth and 16th holes all but rules out the prospect of the Northern Irishman improving on his third-place finish in 2009.
Fowler had no such problems as his eight birdies put him out of sight of the chasing pack.
“It’s long been a dream of mine to win a professional title,” Fowler said. “I want to take the opportunity that I have at the moment.”
Yang, the only Asian to win a major, birdied six holes but bogeys at the third and 17th left the Korean with much to do on Sunday.
Bronson La’Cassie of Australia, also 5 under after two rounds, emulated McIlroy by shooting a 73.