Stale Solbakken's side had not won on Teesside since 1951 although they seemed on course for a point until Marvin Emnes' penalty and Scott McDonald's strike sealed three points for Boro.
Wolves substitute David Davis went close late on with an effort which looked to be heading in until a deflection diverted it into goalkeeper Jason Steele's arms.
The turning point came moments later as referee Robert Madley awarded a spot-kick to the hosts when a cross struck Karl Henry's arm. The visitors were adamant the contact was purely accidental with Henry keeping his arms by his side, but the penalty was awarded and Emnes sent Carl Ikeme the wrong way in the 89th minute.
To rub salt into the wounds, McDonald smashed in a second in the fourth minute of stoppage time as Wolves pushed for a leveller.
The hosts were the first to go close as Luke Williams forced Ikeme into a stop.
Both sides looked more comfortable on the break and Henry's good work almost culminated in a golden chance for the visitors. Henry darted forward down the left and pulled the ball across goal as Jonathan Woodgate had to step with a last-ditch challenge to stop Sylvan Ebanks-Blake sweeping home.
Chances were at a premium although Wolves' Bakary Sako drilled an effort in from range with Steele right behind it.
Boro boss Tony Mowbray tried to inject some life into his side with the double introduction of tricky winger Emmanuel Ledesma and Emnes, and the former jinked inside before firing straight at Ikeme.
At the other end, Kevin Doyle's vicious effort almost caught Steele out with its movement, though the stopper pushed it wide and away from danger.
The visitors looked the more likely to grab a late goal and substitute Davis thought he had clinched three points, but his effort was deflected into Steele's path.
Moments later Boro were awarded a penalty when McDonald's cross struck Henry on the arm. Emnes stroked home the spot-kick and he then turned provider, teeing up McDonald for the hosts' second goal.