Wolves struck two first-half goals as they outplayed Tranmere to return to the top of League One.
The hosts took the lead when top scorer Leigh Griffiths' speculative shot from 25 yards was fumbled in by Rovers goalkeeper Owain Fon Williams for his 12th goal of the campaign.
The home side then doubled their lead on 42 minutes through Dave Edwards.
The fit-again midfielder climbed well to head his first goal of the season from Bakary Sako's near-post corner.
Griffiths was replaced at the break by Jake Cassidy, who came on to face the club where he had spent time on loan in each of the past two seasons.
Cassidy should have scored with his first touch, only to steer his right-foot shot wide with Fon Williams exposed.
On a night when Wolves could have won by more against a Rovers side who had won 5-1 at Coventry on Saturday, Fon Williams saved again with his legs to deny Sako in the dying seconds.
VIEW FROM THE DRESSING ROOM
Tranmere manager Ronnie Moore told BBC Radio Merseyside:
"We've played a super side. They were streets ahead of us and sometimes you just have to hold your hands up.
"You look at their budget and our budget, and that's what you get. I don't think there's any disgrace in coming here and getting beaten.
"Owain Fon Williams has got his head in his hands, but he kept us in the game on Saturday at Coventry with two great saves. That's football. He's just got to get on with it."
Wolverhampton Wanderers 13 Ikeme 18 Ricketts 26 Golbourne 04 Edwards 06 Batth 05 Stearman 27 Jacobs (Price - 86' ) 11 McDonald 09 Griffiths (Cassidy - 45' ) 29 Doyle 10 Sako (Ismail - 89' ) Substitutes 02 Doherty 15 Sigurdarson 16 Cassidy 19 Price 21 Ismail 23 Ebanks-Landell 31 McCarey Tranmere Rovers 01 Williams 02 Holmes 23 Ridehalgh 17 Power (Wallace - 45' Booked ) 20 McNulty 05 Goodison 15 Kirby (Bell-Baggie - 69' ) 14 Atkinson 09 Lowe 22 Koumas (Sodje - 68' Booked ) 26 Akpa Akpro Substitutes 03 Horwood 06 Hateley 08 Wallace 11 Bell-Baggie 12 Rowe 19 Sodje 33 Mooney
Ref: Graham Scott