Raul Jimenez equalised from the spot but had two first-half efforts ruled out by VAR as Wolves had to settle for a 1-1 draw with Southampton.
The Mexican striker twice put the ball in the net in the opening 45 minutes but VAR ruled his first strike out for handball and his second for offside in the build-up.
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Southampton looked to have cashed in on those breaks when Danny Ings pounced on a mistake to fire them in front in the 53rd minute but Jimenez finally got his goal by converting from the spot eight minutes later after Matt Doherty was tripped.
James Ward-Prowse almost pinched it for the visitors with a late free-kick but the draw was enough to end Saints' run of three straight Premier League defeats.
Wolves: Rui Patricio (7), Bennett (4), Boly (6), Cutrone (6), Coady (6), Jonny (7), Neves (6), Moutinho (7), Dendoncker (6), Traore (6), Jimenez (8).
Subs: Ruddy, Doherty (7), Vallejo (4), Jota (7)
Southampton: Gunn (6), Valery (7), Vestergaard (7), Bednarek (7), Yoshida (7), Bertrand (7), Romeu (6), Hojbjerg (7), Ward-Prowse (6), Redmond (6), Ings (7).
Subs: Boufal (5), Danso (n/a).
Man of the match: Raul Jimenez
Wolves remain in the bottom half after a fifth draw in nine games this season.
How VAR could not stop Wolves rescuing point
Nuno Espirito Santo's hosts were hoping to build on the momentum gained from three straight wins, the latest the shock 2-0 victory at Manchester City prior to the international break.
But they failed to find much of a rhythm in the first half as Southampton, who had slipped into the bottom three prior to kick-off following Everton's win over West Ham, looked lively.
Ings had a close-range shot blocked and the visitors looked bright on the break - but the two big moments of the half came at the other end as Wolves were hit twice by VAR.
The first, in the 28th minute, came when Jimenez controlled a bouncing pass over the top with his hand and ran the ball into the empty net after Saints goalkeeper Angus Gunn had come rushing out.
The striker looked a little unlucky as he tried to lean into the ball but VAR said no and Jimenez was also booked for deliberate handball.
While that one looked as if it was always likely to be chalked off, his second effort just three minutes before the break seemed legitimate in full speed.
Jimenez linked up with Leander Dendoncker and Patrick Cutrone in the box and after the latter's shot was parried away by Gunn, he was there to tap into an open goal.
However, VAR spotted that Cutrone was marginally offside in the build-up and the goal was overturned.
After escaping twice, it was Southampton who took the lead six minutes into the second half.
Wolves' young substitute Jesus Vallejo cleared poorly and, when the ball came back in, Conor Coady misjudged the bounce on the edge of the box and Ings was there to pounce, directing a right-foot shot back across the goalkeeper for his fifth goal in four games.
To their credit, Wolves responded quickly and, eight minutes later, another home substitute, Matt Doherty, jinked past a series of Southampton defenders in the box and was tripped by Pierre Hojbjerg.
Despite his earlier disappointments, Jimenez stepped up to take the spot-kick and stroked it home to end a run of six games without a goal.
There was still plenty of time for the hosts to find a winner but they struggled to create anything clear cut and it was Saints who almost stole the points when Ward-Prowse's 88th-minute free-kick was tipped behind by the diving Rui Patricio.
What the managers said
Wolves boss Nuno Espirito Santo: "It was tough, Southampton are well organised, press very well and made it tough to have possession. A lot of things happened during the game, there was a lot of fight for every ball - sometimes it's not what you want to do.
"The second half was better, but the goal was a mistake and then we pushed until the end. You celebrate what seems to be a normal goal, everyone's happy but then you wait and they take it away and Southampton celebrate a non-goal - it's just VAR, we have to get used to it."
Ryan Bennett and Jonny returned for Wolves while Ruben Vinagre dropped to the bench and Romain Saiss missed out with a hamstring injury.
Jannik Vestergaard was the only Southampton change from their humbling by Chelsea, replacing Shane Long as they reverted to a back three.
Southampton manager Ralph Hasenhuttl: "We tried to be committed and have a good balance in our defence, and I think Wolves didn't have too many chances.
"We got in the lead with a good goal, then the penalty was too easy, we didn't defend well at that moment but we must take a point - it's okay.
"It was important after the last three games that we show up, show we can compete and it was a step forward, only a small one."
Man of the match: Raul Jimenez
If at first, you don't succeed...
Raul Jimenez is a proven goal-getter in the Premier League but six games without finding the net will niggle away at any striker. Today, it just didn't seem as if it was his day, the Mexican twice being denied by the all-seeing eye of VAR.
For his first, Jimenez seemed to be making a genuine attempt to control the ball with his chest when being pulled up for handball. A yellow card certainly seemed harsh.
The second was frustrating - although correct - as he started an intricate move and was in perfect position to finish it off. The celebrations were in full flow so that one was hard to stomach.
But Jimenez never gave up and when presented with a chance to pull Wolves level from the spot, he was still cool enough to take a pause, help freeze the goalkeeper, and fire home to earn his side a point.
Analysis: 'It was never a penalty'
Charlie Nicholas on Soccer Saturday:
"It's a bit harsh on Wolves [Jimenez's disallowed opening goal] as the ball just skipped up and hit Jimenez on the arm before his tap in.
"They're saying it's a deliberate handball but it wasn't as the hand was in a natural position. So it was the correct decision to rule it out but the yellow card was harsh.
"Wolves get a penalty though to get level, and it was never a spot-kick. VAR was involved again with Doherty getting inside the box. He and Hojbjerg were both vying for the ball.
"I thought Doherty threw himself into Hojbjerg and the Southampton players were furious. It was a clear and obvious error for me."
- Wolves have lost just one of their last 13 Premier League matches at Molineux (W7 D5 L1).
- Seven of Southampton's eight points this season have come on the road - a league-high share in 2019-20 (88%).
- Southampton's Danny Ings has scored in four consecutive appearances in all competitions for the first time in English football (five goals).
Wolves resume their Europa League campaign with a trip to Slovakia to take on Slovan Bratislava on Thursday. They're back in Premier League action on Sunday, October 27, facing Newcastle at St James' Park, a game that's live on Sky Sports Premier League; kick-off 2pm.
Live Renault Super Sunday
Southampton host Leicester at St Mary's on Friday, October 25 on Friday Night Football, live on Sky Sports Premier League; kick-off 8pm.