Town, fresh from their 3-1 weekend win at Millwall, went into the game on a high, seeking their second successive league double in four days and eyeing an eighth consecutive victory over Wanderers.
But after some desperate days against Town in recent years, Wolves, who had not won against the Yorkshire side in 11 previous meetings since beating them 2-0 in February 1997, claimed some choice payback.
An early Nouha Dicko strike gave them the lead after 12 minutes and an unfortunate own goal 56 seconds into the second half from Conor Coady doubled their lead.
Ex-Town loanee Benik Afobe added a close-range third just after the hour mark after a swift Wolves break - and despite James Vaughan reducing the arrears - after a fleet-footed counter exposed the hosts at the end, with Dicko netting his second of the evening.
Powell took some solace in a host of attempts on goal from Town, who have now suffered back-to-back home defeats for the first time in his tenure, but he admitted that the class of Wolves going forward told in the final analysis.
Powell, whose side visit high-flying Bournemouth on Saturday, said: “We created over thirty-odd chances, but two of the goals were our own doing.
“It was unfortunate for Conor with the own goal and Butts (Jacob Butterfield) is a player who normally doesn’t give the ball away and his pass goes straight to their player and it was a very good pass and in a flash we find ourselves 1-0 down.
“We did have chances and their keeper did make some good saves and there were one or two key blocks, but really looking back, they countered on us very well.
“They have a good team and Kenny has fashioned a good squad and they have spent some money in key areas, like Benny (Adobe), who everyone here knows well.
“I know on any given day in the Championship, you can beat a top side as we have shown this season. But there is a marked difference, no doubt, when you look at the Middlesbrough’s, Derby’s, Wolves and Bournemouth.
“They do seem to be at just another level, which we are aspiring to.”
He added: “To be fair, the players kept going and Sean Scannell, on both sides, worried them. It was end to end and they took more of the chances that fell their way than us.
“I am quite stunned by it all really. But we have to get ourselves ready for Bournemouth and a really tough assignment again.”
Big striker Ishmael Miller was handed a first debut in place of the suspended Nahki Wells alongside Vaughan and Powell felt it was a mixed debut for the forward.
But he is confident that Miller will prove a strong asset to the squad, given time.
He said: “At times, he showed what he has. At other times, it was a little bit difficult.
“We don’t really him (yet) as such. He’s a player who does need the ball into feet and he showed at times he can link up with James Vaughan and the midfield.
“He hasn’t played for a while and of course I was going to leave him on as you need your strikers on the pitch. I am sure we will see a lot more from him.”