Rayan Ait-Nouri gave the hosts a flying start inside two minutes, before a calamitous own goal saw Guglielmo Vicario punch the ball off Djed Spence to make it 2-0.
Twice the Londoners clawed their way back into the contest through goals from Mathys Tel and Richarlison, only to concede immediately after, as Jørgen Strand Larsen and Matheus Cunha restored Wolves' two-goal advantage.
"Funny game because for the most part it was decent, considering the changes we made," Postecoglou told reporters.
"I thought we controlled large parts and were a bit of a threat going forward, but then we've conceded some poor goals.
"We made some individual errors, which is unusual for us, but they all happened in one game. It's not like they are doing it on purpose."
Spurs are languishing in 15th place in the Premier League, with the Europa League now representing their last realistic chance to salvage the season — and potentially save Ange Postecoglou's job.