Rampant Wanderers netted three second-half goals, but they also had to withstand strong pressure from Vale in an entertaining contest.
Vale boss Micky Adams said: "I'd like to congratulate Wolves because we've played against a good team, but what happened today won't define our season.
"We certainly had our moments and at 1-0 there was nothing in it. But at this level you have to take your chances and up to now we haven't taken enough of them.
"I'm going to take a lot of positives from our performance and I was pleased to see Tom Pope get off the mark. He's playing against good defenders who don't like being dominated.
"I would like us to show more desire to keep a clean sheet. We don't look like keeping one at the moment and I was also disappointed with the quality of the crosses we put into the Wolves box. A lot of them made it too easy for their defenders to clear the ball."
Leigh Griffiths scuffed the first clear chance of the game in the first minute of the second half, but the striker made amends by opening the scoring in the 56th minute.
Vale defender Carl Dickinson failed to clear his lines and Griffiths stole the ball in a flash before driving a fierce left-foot shot inside Chris Neal's left-hand post from 14 yards.
The home side responded with gusto as Doug Loft's header from Adam Yates' cross struck a post before Dickinson almost atoned when his volley drew a brilliant save from Carl Ikeme.
But Wolves put the game to bed as substitute Bjorn Sigurdarson and the classy Kevin McDonald netted in the 75th and 83rd minutes respectively.
Substitute Ben Williamson also struck the woodwork for Vale late on before Pope headed an injury-time consolation goal which was very much deserved.