Peter Wright was another high-profile casualty in Hungary as Jim Williams produced an inspired comeback to deny the world champion a winning return in Budapest.
Van Gerwen and Wright were among ten seeds to crash out on a remarkable day of second round action at the BOK Sportcsarnok on Saturday, with Jonny Clayton and Luke Humphries also exiting the tournament.
Top seed Van Gerwen squandered 25 darts at double as his winless run against Whitlock continued, with Australia's World Cup winner registering a nerveless 13-dart hold in the decider to progress.
Meanwhile, Wright was left to rue two missed match darts in an edgy conclusion against Williams, who fought back magnificently from 5-3 down to advance.
Wright, making his first appearance since undergoing gallstones surgery last month, conjured up 160 and 145 finishes to seize the initiative, but skin-saving 125 and 100 checkouts catapulted Williams to an unlikely victory.
Jose De Sousa landed a sublime 11-dart break to clinch a last-leg win over Raymond van Barneveld, after the Dutch legend wired one match dart at double 18 in a dramatic finale.
The opening ten legs went with throw, yet De Sousa - who missed double 12 for a nine-darter in leg four - followed up his sixth 180 by pinning tops to prevail with a 99 average.
De Sousa will now lock horns with Jeffrey De Zwaan on Sunday, after the Dutchman fired in five 180s to topple Rob Cross 6-4 and preserve his Cazoo European Championship qualification hopes.
Boris Krcmar also claimed a crucial win in his bid to qualify for October's main event, winning five straight legs to stun second seed Humphries and set up a showdown with Dave Chisnall in round three.
Chisnall produced two sensational finishes to deny Clayton earlier in the afternoon, following up a 117 checkout in leg nine with a brilliant 135 finish on the bull to seal the deal in style.
Joe Cullen returned to winning ways on the European Tour courtesy of a battling 6-4 win over Martin Lukeman, and the Masters champion now faces Welsh star Williams in the third round.