Gavin Green and Nico Geyger set the clubhouse target as the Belgian Knockout made its European Tour debut at Rinkven International Golf Club.
The innovative format sees the 144-man field play two days of 18-hole stroke play, with the top 64 then advancing to a nine-hole stroke play knockout and the winner being crowned on Sunday after a total of 90 holes.
Green and Geyger are also in their debut seasons on the European Tour and they relieved the pressure heading into Friday and set themselves up for a potentially high seeding at the weekend with opening rounds of 67.
Matthew Baldwin was also at four under having played just seven holes of his first round.
Home favourite Nicolas Colsaerts had a big following in Antwerp and he was just one back alongside English pair Sam Horsfield and James Heath, and Frenchman Benjamin Hebert.
Malaysian Green finished second at last year's Hero Indian Open en route to claiming the Asian Tour Order of Merit, while Chilean Geyger earned his playing privileges via the Qualifying School.
There were a host of players jostling for position in the early stages but Hebert was the first man to get to three under and stay there.
After an opening bogey on the tenth, the Frenchman birdied the 14th, 16th and third, and when he got down in two putts from the fringe on the par five fifth, he was in a share of the lead.
Dane Joachim B Hansen had started with a birdie and made further gains on the 17th and 18th, while Heath made birdies on the 12th, 17th and third to join the pack.
Horsfield then made it a four-way tie as he added to gains on the first and fourth with a long putt on the 17th that saw him join Hebert in the clubhouse.
A ten-foot right-to-lefter on the fourth made Heath the first man at four under but he was soon joined by Hansen who birdied the third.
That was when Green made his move, with gains on the 17th and 18th adding to birdies on the eighth and 12th to set the target.
A bogey from Hansen on the fifth was followed by a triple on the seventh as he fell back, while a dropped shot from Heath on the ninth left Green in the solo lead.
He would not be on his own for long, however, as Geyger came home in spectacular style.
After a bogey on the fourth and a birdie on the seventh saw him turn in 36, the 31 year old picked up shots on the tenth, 11th, 15th and last to surge up the leaderboard.
Colsaerts had delighted the large local gallery following him with birdies on the 16th and 18th, and he made another on the eighth before an excellent par save on his final hole after going right off the tee.
England's Baldwin had birdies on the tenth, 11th, 15th and 16th as he made a fast start.
Scot David Drysdale, Australian Lucas Herbert and South African Erik van Rooyen were at two under, a shot clear of a group of seven players in the clubhouse.