Holmes looked in top form right from the first hole as he fired eight birdies and an eagle to fashion a handsome advantage.
However, while Holmes ended Thursday’s play smiling, the same could not be said for Rory McIlroy as the Ulsterman continued to struggle.
After failing to make the cut at the Honda Classic last week, his first PGA event of the year, Mcilroy would have been hoping for a change in his fortunes at Doral.
However, was once again found wanting as he stumbled his way to a one-over 73, leaving him 11 shots behind Holmes.
Meanwhile, second-placed Ryan Moore stuttered after making an impressive start to his campaign.
Moore kept up with Holmes for most of the day, striking eight birdies before his day fell apart somewhat. The 32-year-old found the water at 18 to finish with a double-bogey six and a round of 66, four shots back from the leader.
France's Alexander Levy and the American duo of Dustin Johnson and Rickie Fowler share third place on the leaderboard following a solid first round on the Blue Monster course.