Colsaerts picked up just one birdie in a solid front nine at the Golf Club Torino and despite a bogey at the par-four 10th the 32-year-old went on to reel off six consecutive birdies.
The big Belgian was par at the 17th and finished with another birdie at the 18th to take the clubhouse lead with Argentina's Ricardo Gonzalez and Germany's Maximilian Kieffer.
Having pulled out of the Dutch Open last week with flu, Colsaerts revealed his speedy recovery was partly down to the tender, loving care of his mother.
"Nothing beats a couple of days at home with your mum looking after you," he said.
"I was sitting on a sofa watching the golf and I was quite happy."
Gonzalez has missed three cuts in a row since finishing runner-up at the Johnnie Walker Championship at Gleneagles but stayed well in contention with six birdies, one bogey and an eagle at the 12th.
"I tried to relax the last two or three weeks but I played with a little tension.
"On Tuesday's practice I said 'come on, relax' and it worked," he said.
"I'm feeling very good and we'll see what happens over the next three days."
Kieffer, who is making a good impression on his European Tour debut, boosted his chances of qualifying for the Dubai World Championship with a good finish this week.
The 23-year-old currently sits 77th and could make the top 60 with a solid finish this week.
Australian Marcus Fraser was a shot behind after a 66, with England's Steve Webster on five under and local favourite Francesco Molinari carding a 68.
Leading scores from the first round of the Italian Open on Thursday at the Golf Club Torino (Gbr & Irl unless stated, par 72):
65 - Ricardo Gonzalez (ARG), Maximilian Kieffer (GER), Nicolas Colsaerts (BEL)
66 - Marcus Fraser (AUS)
67 - Steve Webster, David Higgins
68 - Francesco Molinari (ITA), Joachim B Hansen (DEN), James Kingston (RSA), Richard Finch, Jorge Campillo (ESP), Simon Thornton, Seve Benson
69 - Thomas Aiken (RSA), Edoardo Raffaele Lipparelli (ITA), Estanislao Goya (ARG), Simon Dyson, Johan Edfors (SWE), Felipe Aguilar (CHI), David Drysdale, James Ruth, Andreas Harto (DEN), Bernd Wiesberger (AUT)
70 - Soren Kjeldsen (DEN), Robert Coles, Matteo Manassero (ITA), Jaco Van Zyl (RSA), Tom Lewis, Mikko Korhonen (FIN), Simon Wakefield, Graeme Storm, Emiliano Grillo (ARG), Julien Quesne (FRA), Mark Tullo (CHI), Retief Goosen (RSA), Matthew Nixon, Espen Kofstad (NOR), Kristoffer Broberg (SWE), Maarten Lafeber (NED), Lee Slattery, Justin Walters (RSA), Alexander Levy (FRA), Chris Lloyd
71 - Jose-Maria Olazabal (ESP), Niclas Fasth (SWE)