Robin Knoche, Vieirinha, Naldo and Stefan Kutschke scored the goals for Dieter Hecking's men as they dismantled the Royal Blues at the VW-Arena.
Schalke had just one really good chance in the first half, but capitulated under the pressure in the second 45 minutes, going down to a defeat which leaves them with just a point from their first two games of the Bundesliga campaign.
Wolfsburg coach Hecking gave Gustavo an immediate debut just 24 hours after he arrived at the club from Bayern Munich.
There was a debutant in the Schalke side too with former Borussia Dortmund defender Felipe Santana starting at the heart of their defence.
He was caught off guard by a deflected cross which teed up Ivica Olic for the first chance of the game in the 26th minute, but the Croatian's effort landed on the roof of the net.
Ten minutes later, Vieirinha wasted a glorious opportunity to put the Wolves ahead when he met Ricardo Rodriguez's cross on the volley at the far post, but he made a poor connection with the ball and sent it wide.
Klaas-Jan Huntelaar made a somewhat better contact to his shot in the 40th minute, but the post denied the Dutchman.
Wolfsburg took the lead in the 55th minute and the floodgates opened.
Ivan Perisic nodded the ball on into the middle from a corner and Knoche was given enough room to stick a leg out to turn it in.
Five minutes later, Vieirinha picked the ball up on the edge of the penalty area and, after skipping past Christian Fuchs, he sent the ball low into the far corner of Timo Hildebrand's goal.
Defender Naldo made it three midway through the second half, turning a volleyed cross from compatriot Diego goalwards and pouncing when Hildebrand parried his first effort.
Schalke lost the will to fight and they lost another goal in stoppage time when Kutschke marked his Bundesliga debut with a goal, turning Marcel Schafer's cross through Hildebrand's legs to give Hecking the home win he wanted.