Aided by birdies on 10, 14, 16 and 17 on Royal Troon's tricky back nine, the 46-year-old American posted a 63, equalling the record low for majors first set by Johnny Miller in the 1973 US Open.
Mickelson came within a fraction of an inch of breaking the record outright. His curling 15-foot putt for birdie circled the hole on 18 before settling just outside it.
"That putt on 18 was an opportunity to do something historical," Mickelson said at a news conference. "I knew it, and with a foot to go I thought I had done it... and then I had the heartbreak that I didn't and watched that ball lip out. It was, wow, that stings."
It was still good enough for an eight-under effort and a bogey-free round, and it put him three ahead of compatriot Patrick Reed and Martin Kaymer of Germany.
All three seemed to be well-positioned for the second day, but Kaymer at least was not getting ahead of himself.
"It's only a quarter of a marathon..." he said. "It's a good start, It's a very good start. But tomorrow we'll see how the weather will turn out and then play another good round. That's all you can do."
Reed's early 66, a round punctuated by an eagle from the fairway on the par-four third hole, set the clubhouse lead for much of the day. He has no intention of changing his approach, although the weather is forecast to turn wet and cold after Thursday's warm sun and gentle winds.
"My game plan is to play to certain areas on each hole," he said. "I'm not really going to stray too far away from that. It's just going to probably determine what club off the tee. Some holes today might have been a 4-iron, but if the wind is howling, it might be a 2-iron ... you just never know."
Just behind Reed and Kaymer were a shifting cast of players who kept threatening and the falling back throughout the day, making four-under a bar that was hard to clear.
Rory McIlroy and Bubba Watson, among others, advanced to four or five-under and then retreated.
