Marcus Smith proved the difference for dogged Harlequins as they deservedly put an end to Sale's unbeaten start to the Premiership season at the AJ Bell Stadium.
England fly-half Smith scored 24 of Quins' 29 points as a resolute defensive effort kept previously high-scoring Sale at arm's length.
Quins' 29-13 triumph - their third win of the campaign - will surely be one of head coach Tabai Matson's most satisfying yet after Nick David's early try had got the ball rolling in Manchester.
Both teams had tried to make some enterprising breaks by the time Quins broke through in the 11th minute.
Sharks' defence had been standing firm until that point, but a quick break and a tidy kick forward by Smith - on his 100th Premiership appearance - bounced favourably for David, who just about got over in the corner. Smith obliged with a difficult kick, which went over off the post.
The Sharks were soon level, however, with some terrific work from Raffi Quirke carving an opening for Sam James, who was able to charge through under the posts unopposed. Rob du Preez could not miss the conversion.
Suddenly the game had burst into life, and minutes later a Du Preez penalty edged Sale 10-7 ahead. Some expansive play by Danny Care eventually led to Quins earning a penalty chance, and Smith was classy with an effort from distance to even it up again.
As half-time approached both sides were enjoying their share of possession, only for the odd loose pass to halt the momentum.
It was a superbly-worked try which sent Quins in at the break with the advantage. Quick hands through the backs from left to right culminated with Care whipping the ball to Smith, who darted in close to the posts. Smith's precise boot ensured Matson's battlers went in at half-time leading 17-10.
Smith's accuracy came to the fore early in the second period, as his penalty attempt from distance sailed right down the middle to make it 20-10. Sharks replied through Du Preez, however, and within seconds the gap was down to seven again.
This was growing into an intriguing clash as both teams continued at a relentless pace in trying to up their bid for supremacy, though it was another Smith penalty which helped keep Sale at bay with 25 minutes left.
Quins now had the upper hand and looked to be homing in on what would be an eye-catching victory, and more Sharks indiscipline allowed Smith another chance to pop over a penalty from long range. Again he made no mistake to extend the visitors' lead to 26-13.
When the man of the moment kicked another penalty to extend the lead to 16 points with nine minutes to go, it now looked like Sale's game was finally up.
The hosts threatened late on but Quins held on for a deserved victory to move up to fifth in the Premiership table.
