Jack Harrison, Luke Ayling, Rasmus Kristensen and Rodrigo pounced for the visitors as they escaped the Premier League relegation zone.
Jonny spectacularly snatched a goal back before Matheus Cunha made it 3-2 but Jonny was then sent off for a dangerous tackle on Ayling.
Unused substitute Matheus Nunes was also dismissed for an altercation with he assistant referee in the aftermath of Rodrigo's goal, with Wolves angry it was allowed after Adama Traore was pulled back by Marc Roca in the build-up.
Wolves also felt they should have had a first-half penalty after Nelson Semedo went down under Junior Firpo's challenge.
Wolves have had three apologies from PGMOL chief Howard Webb in the last two months for refereeing errors and only on Friday Lopetegui said he still trusted the officials.
"I can make a book (about bad decisions) - Liverpool, Nottingham Forest, Newcastle, Southampton, today," said Lopetegui, who arrived for his press conference 90 minutes after the final whistle while colleagues Edu Rubio and Matt Wild visited referee Michael Salisbury after the game.
"Sometimes you can understand mistakes, they are part of football, but to repeat the same mistake against us is not easy.
"I don't want an explanation, I'm not waiting for one. In the last match (against Newcastle) it was the same, today again.
"I want to have fair decisions and not have the sensation or the feelings it was unbalanced. At the end of the season normally they are going to be balanced but we are very unlucky, we have to be critical with the bad things but we didn't deserve to lose this match.
"We had a very clear penalty again but the referee and VAR thinks the opposite."
Lopetegui said Wolves intend to appeal against both red cards.
"Jonny's red card, in the last touch he lost a bit of control. I think it's a yellow," he said.
"After their fourth goal it was a very clear foul on Adama, and Nunes wanted to complain. He was walking back, the linesman bumped into Nunes, he couldn't see him. He didn't have any intention."
Harrison opened the scoring after six minutes from Wilfried Gnonto's cross but Wolves rallied, only for Pedro Neto to scuff a fine opening while Semedo saw a shot blocked.
Wolves thought they had equalised when Mario Lemina prodded in but he was correctly ruled offside before Ayling made it 2-0.
It got worse for Wolves after 61 minutes when Kristensen, who had only been on 31 seconds, robbed the dawdling Jonny and fired through Jose Sa's legs.
Jonny started to atone for his error three minutes later when he lobbed into an empty net from 40 yards.
Illan Meslier denied Cunha but was wrong-footed when the striker's shot deflected off Max Wober to make it 3-2.
But Jonny's red card for a dangerous tackle on Ayling with six minutes left ended Wolves' comeback.
Rodrigo added a fourth in stoppage time when he raced clear with the hosts furious Roca had not been penalised. Nunes was sent off after appearing to collide with the linesman and was dragged away.
Leeds' only other away league win had come at Liverpool in October but they climbed out of the relegation zone to sit 14th, a point behind their hosts.
"We got a very good win, our players did an amazing game and they deserve the reward and the three points," said boss Javi Gracia.
"If we analyse the game I'll tell you we have to improve many things. Defending we can do better. We were playing against a very good team with very good players.
"Now we have time to enjoy the win and we can prepare with more confidence.
"You know the points are really important and you need them. There are 11 games left and all the games are like a final for us."