Ruben Loftus-Cheek, handed his first league start of the campaign, had put the Blues ahead in the 18th minute with a heavily deflected effort - his second goal in four days after netting in Sunday's 2-0 win over Fulham.
It looked as though his contribution could prove decisive until the host struck twice in four minutes at a raucous Molineux.
Raul Jimenez brought the scores level, his rasping finish from a narrow angle proving too hot for Kepa Arrizabalaga and the comeback was complete when Matt Doherty's low cross to the far post found Diogo Jota unmarked to tap home.
The fightback consigned Chelsea to successive Premier League away defeats and left Maurizio Sarri with much to ponder ahead of welcoming leaders Manchester City to Stamford Bridge.
Eden Hazard, without a goal in two months, saw a pair of half-chances come and go in the opening seven minutes but the Blues did not have to wait long for a breakthrough.
It arrived with a healthy slice of fortune, however, as Loftus-Cheek's effort looked to be heading straight for Rui Patricio before Conor Coady's unwitting intervention with his head wrong-footed his goalkeeper.
Patricio superbly tipped Willian's free-kick over as Chelsea sought a swift second, although Cesc Fabregas had to throw himself into a desperate block to thwart Morgan Gibbs-White at the other end.
Ryan Bennett and Willy Boly produced similarly heroic last-ditch challenges to deny Willian and Alvaro Morata either side of the break, and those interventions took on added importance as Wolves struck twice in quick succession around the hour through Jimenez and Jota.
Chelsea fought to find a way back, Hazard and Fabregas firing over in the closing stages, but Nuno Espirito Santo's men held on to claim a famous win and snap a worrying sequence that delivered just one point from six matches.