After a goalless first half, Olivier Giroud continued his fine form by firing through Rui Patricio to give the Blues the lead.
Daniel Podence restored parity midway through the second period when his deflected effort flew past Edouard Mendy, before Pedro Neto earned Wolves a huge three points in the fifth minute of stoppage time by firing across the Senegal international into the far corner.
Nuno will hope that a brilliant win and performance against a title contender will boost his squad's morale, ahead of tough games against Tottenham and Manchester United to come over the Christmas period.
Solid Wolves look comfortable in natural back three
For the first time since the timid and cautious display against Leicester before the November international break, Nuno set his side up in his preferred three-at-the-back system.
Willy Boly returned to the side and took his place alongside Conor Coady and Romain Saiss for the first time since the 4-0 defeat to West Ham in September.
With one more body in defence against Chelsea's potent attacking force, Wolves looked far more solid than they had in their two previous games against Liverpool and Aston Villa. Aside from an individual error by Boly for Giroud's goal, Wanderers looked in control at the back and dealt well with multiple Chelsea attacks.
After poor defensive displays with square pegs in round holes in recent weeks, it looks as though a back three could return for good.
Podence and Neto prove their worth with match-winning displays
Since Raul Jimenez suffered his sickening fractured skull at the Emirates Stadium two-and-a-half weeks ago, fans and pundits alike have been wondering where Wolves' goals will come from in the Mexican's absence.
Against Chelsea, Daniel Podence and Pedro Neto provided the answer. The Portuguese wingers provided the latest in a lengthly list of brilliant performances this season, and for the second time in four games, sealed a 2-1 win with a goal apiece.
Neto in particular came into his own in the final 20 minutes and continuously drove at a Chelsea defence that simply couldn't contain him. The 20-year-old burst through the gap between Reece James and Kurt Zouma on countless occasions late on, with the last of these runs winning the game for Wolves in the 95th minute.
If Neto and Podence continue to perform as they did against Frank Lampard's side, questions about Wolves' goal return will quickly subside.
Otasowie impresses on Premier League debut
After a relatively solid first-half performance, Nuno made a rare half-time substitution and gave Owen Otasowie his Premier League debut in place of Leander Dendoncker.
The 19-year-old, who had made one previous first team appearance as a substitute in last year's 4-0 Europa League win over Besiktas, will have impressed Wolves fans as he slotted in seamlessly alongside Ruben Neves in midfield.
Otasowie gave the performance of a seasoned veteran, completing 81% of his passes, making two tackles, four interceptions and winning six duels, as well as providing the assist for Podence's equaliser.
Having made his USA debut against Wales in last month's international break, Wolves look to have a real talent on their hands and will hope for more of the same from the young man.