Harrison Frazar, John Maginnes, Alex Cejka and Barry Cheesman each carded rounds of 6-under-par 66. Craig Stadler, who won the Senior Players Championship last weekend, and youngster Ty Tryon are among 15 players tied one-stroke further back at minus-5.
Lowery got going on the back nine of En-Joie Golf Club with a birdie on the par-4 10th. He moved to minus-3 thanks to a 25-foot eagle on the par-5 12th, but trouble loomed.
'I got off to a good start,' Lowery said. 'The eagle at the 12th gave me some early momentum.'
The two-time winner on the PGA Tour struggled to a bogey on the par-4 13th after his drive found some trees. He recovered that lost stroke with a birdie at No. 16.
Around the turn, Lowery really caught fire. He moved to 4-under with a birdie at the second. The 42-year-old then rolled in a 10-foot birdie at the par-3 fourth and quickly followed that up with a birdie at the next.
Lowery drained another birdie putt on the par-4 sixth and made it four straight when he rolled home a 25-foot birdie putt at the par-3 seventh.
'I played a lot better than I have been,' said Lowery. 'I went back to my basics. I am surprised I played this well early on.'
Frazar had a chance to own second place by himself but a pair of bogeys on the back side cost him that chance. He started quickly with back-to-back birdies from the third. He then skyrocketed up the leaderboard when he ran off four straight birdies from the sixth to make the turn at 6-under.
On the back side, Frazar dropped a shot when he bogeyed the par-4 11th. He came right back to birdie the next however. The University of Texas alum moved to 7-under with a birdie at the 16th but fell back into a share of the lead with a bogey at the next.
Maginnes began a bogey-free round on the back side where he birdied two of his first three holes. After that, he picked up his third birdie at the 15th. Around the turn, Maginnes drained consecutive birdies from the fifth and capped his round with his sixth birdie at the par-5 eighth.
'I had not broken par since the Capital Open,' said Maginnes. 'Its nice to get off to a good start like this. I've been working really hard lately.'
Cejka also began on the back nine and he sank two straight birdies from the 11th. However he dropped a shot at the 13th. He closed out his first nine with birdies on Nos. 16 and 18.
He made it two straight with a birdie at the first. Cejka then birdied two of the three par-5s on the front side. He two-putted for birdie on the fifth and capped his round with a 10-foot birdie putt at the eighth.
Cheesman sank back-to-back birdies from the second to open his round. He took advantage of the par-5 eighth with another birdie. He rolled off three consecutive birdies from the 10th to get to 6-under. However, he dropped a shot at the 13th, before getting back into a share of second with a birdie at the 16th.
Defending champion Spike McRoy carded a 4-under-par 68. He is among a large group tied for 21st.