The 28-year-old was playing his first competitive round in five months due to the coronavirus pandemic which caused a reshuffle of the European Tour schedule.
Pieters decided not to take part in the first three events of the six week UK Swing as he became a father for the first time to daughter Florence during the four month hiatus.
And the four time European Tour winner had more to celebrate as he showed no signs of ring rust to card eight birdies and one bogey and finish one stroke clear of Toby Tree and Australian Jake McLeod at seven under par at The Celtic Manor Resort.
"It was pretty good. I putted well and kept my ball in play, so I didn’t really get myself in trouble," Pieters said.
"It was tough pulling clubs sometimes and I put some new grips on which were very slippery, so I was struggling with that all day.
"It has been fantastic. I miss my little baby girl, but I am thankful I can play golf right now. It is the first event in five months, so it feels nice to get out there and actually put a score down."
Pieters, the highest ranked player in the field, carded the only bogey of his opening round at the second hole but had to wait until the sixth to pick up his first shot and moved to one under with a birdie at the seventh.
However, it was on the back nine when the Belgian shone with successive gains at the tenth and 11th to get to three under.
He rolled in from six feet for birdie at the 14th before holing another at the next from ten feet to sit one shot behind early clubhouse leader Tree and Swede Sebastian Soderberg at the top of the leaderboard.
Soderberg jumped ahead to seven under at the 15th courtesy of his eighth gain but Pieters was only one behind, alongside Tree, after a terrific chip in from the rough on the par three 17th following a wayward tee shot.
Moments later, Soderberg dropped a shot at the 16th to make it a three way tie for the lead at six under but when Pieters chipped to within two feet at the last and rolled in the birdie putt to come home in a stunning 29, he took the outright lead.
Tree went out in the second group on the opening morning of the tournament and picked up a shot at the first, only to hand it back with his sole bogey of the day at the next.
The World Number 664 continued his momentum following a top 45 finish at last week's English Championship with birdies at the eighth and ninth to get to three under par.
Another gain at the 11th from 15 feet moved him clear at the top at four under and when he carded a three at the par four 15th, his lead grew to two shots.
Soderberg, Australian Min Woo Lee and Belgium's Nicolas Colsaerts closed in to within one shot of the Englishman but Tree restored his two stroke advantage with his seventh birdie of the day at the par three 17th for a six under par 65 before Pieters nudged ahead.
McLeod began his round in similar fashion to Tree, opening with a gain before handing the shot back at the sixth.
The 26-year-old began a birdie blitz from the ninth where he picked up further shots at the 11th, 12th, 14th and 15th to sit two adrift of the leader.
A bogey at the 17th dropped him into the huge pack at four under but he responded in style as he carded one of only five eagles at the last on the first day to jump alongside Tree in second place.
Italian Edoardo Molinari, who was part of Team Europe's Ryder Cup winning team at this venue ten years ago, enjoyed a first round 65, with Soderberg - who carded a bogey-par-bogey finish - Spaniard Nacho Elvira and American Sihwan Kim, compatriot Guido Migliozzi, Scot Marc Warren and Adrian Meronk also at five under.
Colsaerts, fellow Belgian Thomas Detry, Dutchman Wil Besseling, Italian Lorenzo Gagli and English septet Dave Coupland, James Morrison, Matthew Southgate, Andrew Johnston, Sam Horsfield, Steven Brown and Aaron Rai were all locked at four under in Newport.