Americans Lucas Glover and Joe Ogilvie, Australian David McKenzie and Sweden's Daniel Chopra were tied at the top after rounds of 66. Mickelson, Vijay Singh and Davis Love were among a group of six at 67.
Tiger Woods looked shaky -- hitting three tee shots on the par-five 15th -- on his way to a one-over 72.
"It was a fun round today," said Mickelson, who rebounded from a bogey-bogey start due to some poor shots around the green at the 7,326-yard Cog Hill course. "I'm hitting the ball much better."
Mickelson nearly had a double-eagle on the 600-yard par-five ninth when his 4-wood approach from 271 yards out trickled past the right edge of the cup. The reigning PGA and Masters champion rolled in the eight-foot putt for eagle to complete his round.
"It's fun to finish a round of golf like that," Mickelson said.
He added that the work he had put in to prepare for The Open at Hoylake this month had paid off.
"This last week I really started to get tuned in and hit it much better," Mickelson told reporters after his round. "I didn't feel like I played very well a couple weeks ago. I haven't really struck it the way I wanted to since The Masters."
Woods, who missed his first cut in a major as a pro last month at Winged Foot, narrowly missed a slew of putts early on, struggled with his irons and lost his feel from the tee late in the day.
At the 519-yard par-five 15th, Woods pushed his drive way right into trouble and then hit a provisional ball off the tee.
When a spectator helped him locate his first shot deep in the shrubs, Woods declared the ball unplayable and had to return to the tee to hit his third shot on the way to a bogey-six.
"I hit a lot of beautiful putts that didn't go in early and didn't really have control of my irons today," said Woods.
"I know what I'm doing wrong. I'm just having a hard time stopping it," he said, blaming his troubles on the release point of his swing.
"Welcome to golf."
Woods ended on a positive note that brought him a smile when he rolled in a 10-footer for birdie on 18 and finish his 72.
Ten players were tied at 68 on a beautiful day for scoring, including Australian Stuart Appleby, Canadian Stephen Ames, K.J. Choi of South Korea and American Tim Herron.
Defending champion Jim Furyk was among 22 players tied at 69.