The Northern Irishman, 38, carded 10 birdies, eight in his first 11 holes, to join Swede Sebastian Soderberg at the top of the leaderboard.
The pair lie one shot ahead of Zander Lombard of South Africa.
Hoey missed an eagle putt at the ninth and a birdie attempt at the 10th as he attempted to post a first sub-60 round.
Despite passing up those opportunities, his round of 61 was still the lowest of his career.
"I left it in the jaws, both putts, but I was nervous," said Hoey, who has won five times on the European Tour but lost his card last year.
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"It was hard to hit them past the hole but it's nice to be nervous because I haven't been nervous on a golf course for quite a while and it's exciting to have such a good score.
"My best ever score by two shots, no bogeys, it doesn't get much better.
"We've had two kids (since 2013) and it's been tiring. I had to have sinus surgery done a couple of years ago. I haven't been as healthy as I wanted to be, so hopefully now I can get going."
Playing in just his 15th European Tour event after gaining his card via the qualifying school last year, Soderberg was also eight under par after 11 holes and admitted breaking the magical 60 barrier was very much on his mind.
"That's all I thought about walking down the par-five 12th, it kind of helped keep me going," Soderberg said.
"I didn't feel like it stopped me, I definitely had a couple of putts the last seven holes that could have gone in, but overall it was a great round."
Alvaro Quiros, Sebastian Heisele and Jbe Kruger all lie joint third on eight under.
Michael Hoey is tied for the lead at the Rocco Forte Open in Verdura after posting a first round of 10-under-par 61 in Sicily on Thursday.