Sale fashioned a superb late fightback as tries from Mark Cueto and Kyle Tonetti left Harlequins still searching for their first Aviva Premiership Rugby victory of the season.
First-half scores from George Lowe and Jordan Turner-Hall put Quins 17-6 ahead at the break but the momentum was largely with Sale in the second half. Cueto's 68th-minute try was well merited and, after the visitors lost Tomas Vallejos to the sinbin, Tonetti touched down a neat kick from Nick Macleod to seal victory in the closing stages.
Mike Brewer's men deserve immense credit for refusing to buckle against a lively Quins outfit, who themselves showed admirable character before caving into the incessant late pressure.
Both sides were hit by the loss of their first-choice scrum-halves after Dwayne Peel and Danny Care withdrew late on through illness and an ankle injury respectively. The visitors looked more dangerous with the ball in hand during the opening exchanges and they duly led inside the fifth minute when Lowe grounded in the left corner and Nick Evans added the extras from the touchline.
Macleod spurned the opportunity to get Sale off the mark when his long-range penalty attempt sailed wide, but both teams were keen to run the ball at every opportunity.
Sale went agonisingly close to breaching the Harlequins line in the 17th minute when Sosa Koyamaibole's astute offload sent Mark Cueto scampering clear down the left flank before some desperate last-ditch defending denied the England wing.
Moments later Macleod kicked a penalty for Sale and then added another from 60 metres to put his side firmly on the front foot. Yet as the first half wore on, Harlequins grew as an attacking force, largely due to Mike Brown's willingness to break forward from full-back, and a penalty from Evans put them 10-6 ahead in the 28th minute.
Ten minutes later they claimed their second try when Brown glided past a clutch of Sale defenders and broke clear from inside his own half. He was eventually tackled but Turner-Hall remained alive to the possibilities and hacked the loose ball forward before grounding for a try which Evans converted.
Sale head coach Brewer made three changes at the break with Andrew Sheridan, Neil Briggs and Will Cliff replacing Jack Forster, Marc Jones and Chris Leck as the hosts sought to claw their way back into the game. The early signs were encouraging but Sale struggled to make their momentum pay as Quins defended stoutly before losing centre Ollie Smith to the sinbin in the 50th minute for persistent infringement.
Evans threatened to scamper clear for a breakaway score in the 52nd minute only to be denied by a fine tackle by Ben Cohen. Yet the pendulum began to swing back in Sale's favour as the match wore on and incessant pressure led to Vallejos being sin-binned and Cueto touching down in the left corner with 12 minutes remaining after slick handling from Cliff, Macleod and Cohen.
Macleod's conversion attempt rebounded off a post but he soon produced a teasing grubber kick which Tonetti grounded to send Edgeley Park into raptures. Macleod converted the try and then added a late penalty to give Sale their second successive home win under Brewer and leave Quins utterly deflated.