The hosts took the lead in the 15th minute when they won a free kick 20 yards out, Barry Douglas curling his set piece beyond the grasp of Andy Lonergan in the Leeds goal.
Just before the half-hour mark, Nuno Espirito Santo's charges doubled their advantage courtesy of a flowing team move capped off with Ivan Cavaleiro's powerful shot, which went in via a slight deflection.
The visitors improved after the break and halved the deficit early in the second half when Samuel Saiz showed great vision to tee up Ezgjan Alioski, who volleyed home from 10 yards.
Just when Leeds were threatening to get back into the game, however, they found themselves down to 10 men, with Ronaldo Vieira shown a second yellow card for a clumsy foul on Diogo Jota.
The pendulum subsequently swung back the way of Wolves, with Jota racing clear of the opposition defence and dinking the ball over Lonergan on 72 minutes to extend the hosts' lead.
Four minutes later, the contest was all but over after the Leeds goalkeeper brought down Leo Bonatini in the box and Helder Costa converted the penalty to confirm all three points for Wolves.