The 36-year-old Texan piled up eight birdies on the way to a flawless eight-under-par 62 on a relatively calm morning at iconic Colonial Country Club, matching the lowest first round ever recorded at the long established PGA Tour event.
Palmer, who began his round at the par-four 10th and ended it with a five-foot birdie putt at the par-four ninth, surged to the top of the leaderboard, a stroke in front of compatriot John Rollins.
Morgan Hoffmann, a PGA Tour rookie who tied for fifth at last week's Byron Nelson Championship, carded a 64 to finish the day level with fellow American John Peterson and Canadians David Hearn and Graham DeLaet.
"I drove it almost perfect today," Colonial club member Palmer told Golf Channel after matching the 62s previously posted in the tournament's opening round by Patrick Sheehan (in 2005), David Toms (2011) and Chez Reavie (2011).
"I hit the driver really well and when I got out of position, I hit some good shots. If you're going to hit driver a lot, you'd better hit it straight and on a lot of these holes I was able to do that today.
"When I hit it within five or six feet, I made the putt. I had a great day of putting and drove it really good."
Palmer, a three-times winner on the PGA Tour whose most recent victory came at the 2010 Sony Open in Hawaii, kick-started his round at the par-four 14th with the first of four consecutive birdies.
"I made about a 15, 20-footer on 14 which got me going and then I hit it close coming in," he said after making five of his eight birdies from no more than seven feet.
"Then I made some good birdies on the front nine, my back nine. It's a golf course that I am just comfortable on," added Palmer, whose caddie James Edmondson is a three-times club champion at Colonial. "James and I play here numerous times."
World number 13 Matt Kuchar, the highest-ranked player in this week's field, opened with a 65 to end the round level with fellow Americans Daniel Summerhays, Matt Every, Tommy Gainey, Josh Teater and Jordan Spieth.
Zach Johnson, who beat fellow American Jason Dufner by one shot to clinch last year's Crowne Plaza Invitational, launched his title defence with a 69 while Dufner returned a six-birdie 67.
Former Masters champions Charl Schwartzel of South Africa and Angel Cabrera of Argentina opened with matching 70s while three-times major winner Vijay Singh of Fiji carded a 74.
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