Palmer is a member of the Colonial Country Club, which first hosted this event in 1946. Of all the tournaments on the PGA Tour, only the Masters has been played for a longer period of time on the same course.
With only a slight breeze with which to contend, Palmer played a bogey free round. He birdied four straight holes beginning with the par-4 14th.
He had a one-shot lead over John Rollins and a two-shot cushion over Morgan Hoffmann, David Hearn and Graham DeLaet.
Among those tied for sixth at 5-under 65 were Matt Kuchar, Tommy Gainey and 19-year-old Jordan Spieth, who began the year without any playing status on the tour but has all but guaranteed full-time membership for next season.
There were 72 sub-par rounds shot in the opening round and Palmer's score equaled the lowest ever posted over the opening 18 holes.