It was the 17th straight round in the 60s at TPC Deere Run for Johnson, who grew up roughly 100 miles away in Cedar Rapids, Iowa.
Matt Bettencourt made the field as a late alternate and shot a 6-under 65. He's tied for second with former BYU golfer Daniel Summerhays and Brendon de Jonge.
Boo Weekley is among a host of players at 5-under 66, while three-time tournament champion Steve Stricker is at 4-under 67 heading into Friday's second round.
"It's hard to believe that it's been a year. Yeah, I just kind of felt like you're just leading into the next round here," Johnson said. "I've just gotten so used to just everything about this tournament."
It wasn't always that way for Johnson.
Johnson finished 69th here five years ago after shooting 75 and 71 in the final two rounds but he hasn't touched 70 since.
Johnson, who was second in 2009 and third in 2011 before winning last year, topped his final-round 65 of 2012 by one stroke Thursday. He avoided bogeys while picking up birdies on five par-4s.
"It just feels so natural now," Johnson said. 'It just feels very, very comfortable, much like my golf game though I don't want to get overly content with the fact that I'm overly comfortable. So I've still got to go to work."
Villegas was also very comfortable on a course that proved player-friendly in the morning session. He converted a pair of par-3 birdie putts to highlight a strong day on the greens.
Angela Stanford and Catriona Matthew shot eight-under 63s to share the first-round lead at the Manulife Financial LPGA Classic in Waterloo, Ontario, two strokes ahead of top-ranked Inbee Park.
Park is trying to become the first golfer to win four straight LPGA Tour events since Lorena Ochoa in 2008.
Park was joined by American Irene Cho, Spain's Belen Mozo and South Korea's Hee Young Park and Meena Lee at 65.
John Deere Classic
Zach Johnson -7
Camilo Villegas -7
Brendon de Jonge -6
Matt Bettencourt -6
Daniel Summerhays -6