Fellow American Scott Piercy was best among the early starters with a blistering, bogey-free round of nine-under-par 63 for a three-shot lead at the Golf Club of Houston.
Mickelson, the 2011 Houston winner, likes to sharpen his tournament play the week before the test at Augusta National and got off to a fast start.
Beginning his round at the 10th, Mickelson birdied three of his first four holes and added two more birdies to make the turn in five-under 31. He got to seven-under before taking a bogey at the finish when he failed to get up-and-down from a bunker.
Charles Howell III and Luke Guthrie were also in the clubhouse with 66s.
Piercy, who also started on the back nine, used an even hotter streak to take charge as he ran off five consecutive birdies from the 18th and capped off the round with a birdie at his last hole.
Grouped in the clubhouse at five under par were France's Victor Dubuisson, Canadian Graham DeLaet and 2012 winner Hunter Mahan.
Sweden's Jonas Blixt, American Patrick Reed and 2009 champion Paul Casey of England were included in a large group at four-under.
Original source: Mickelson makes solid start in Houston