The hosts showed three alterations to the side who drew 1-1 with Arsenal last weekend, with Maximilian Kilman, Ruben Vinagre and Pedro Neto starting in place of Romain Saiss, Jonny Otto and Diogo Jota.
Wolves won the meeting of the two sides in Slovakia 2-1 a couple of weeks ago, with Romain Saiss and Raul Jimenez their goalscorers.
Early on Kenan Bajric missed a close-range chance for the visitors, who were then indebted to keeper Dominik Grief as he kept out a deflected Joao Moutinho shot.
Just past the 20-minute mark Slovan skipper Vasil Bozhikov made a crucial intervention close to his own goal-line, heading clear with Jimenez closing in.
The remainder of the first half saw the hosts struggle to break down a resolute visiting backline, with Kilman heading a rare opening wide just before the interval.
Wolves had the perfect opportunity to break the deadlock straight after the restart as Bozhikov sent Neto crashing in the area, but Grief got down well to his right to keep out the resulting spot-kick from Ruben Neves.
The Slovan keeper then made a fine save to deny Jimenez, after the Mexico frontman had turned away from his marker and volleyed goalwards after receiving a pass from Moutinho.
Neves tried his luck with a trademark long-distance drive, but again Grief was equal to the task and soon after there was a lengthy halt to play as Bajric was caught in the face by Jimenez.
And it was Jimenez who was to finally break the deadlock in stoppage time, heading home from a cross delivered by Adama Traore from the right-hand side.