Having notched their first win of the season against Saracens last weekend, the Quins grabbed their opening away success with a backs-to-the-wall performance against an under-performing Sharks outfit.
Fly-half Jeremy Staunton stole the show for the visitors, slotting four penalties out of four in a flawless kicking display as Sale lost a great opportunity to close the gap on leaders Leicester.
The Sharks, missing a host of key players either on international duty or through injuries, had the first opportunity to open the scoring – but fly-half Byron Hayward missed a relatively simple penalty from 35 yards.
Within a minute they had conceded a try.
Quins' scrum-half Steven So'oialo made an electric break down the left, and the Samoan international fed flying winger Simon Keogh who touched down under the posts for his second try of the season. Staunton converted.
A shell-shocked Sale finally got to grips with the game and hit back when Hayward slotted a penalty.
The Welsh number 10 then missed another penalty – and it was left to Staunton to show Hayward how to do it at the other end, with a three-pointer of his own to increase the lead to 10-3.
Despite dominating possession, the Sharks' back play was often clumsy. But their forwards were providing the penetration, and Quins soon paid the price for their ill-discipline.
Former South Africa captain Andre Vos was sent to the sin-bin for a calculated offence on their own try line. The visitors were soon down to 13 men, Staunton given a second yellow card for a blatant offside.
But despite being camped in their own 22 and under a barrage of attacks, the Quins' defence held firm.
The home crowd could finally celebrate when Kiwi centre Robert Todd cruised over on the flank. Hayward converted to bring the scores level, just as Vos made his return from the sidelines.
Harlequins, having soaked up piles of pressure, somehow went into the interval in the lead when Staunton notched a penalty on the half-time whistle to make it 13-10.
The 24-year-old Irishman slotted over a long-range penalty to extend the advantage at the start of the second half, but the opening exchanges were marred by sloppy handling and attacking indecision.
An increasingly demoralised Hayward missed yet another penalty, as Sale's inability to finish off phase after phase of possession football was again apparent.
The stand-off managed to knock over a close-range three-pointer, his second of the night, to narrow the deficit – and the Sharks were certainly on the front foot as Quins fought hard to defend their slender lead.
Quins hit back, and Samoan wing George Harder cut through the home defence only to be held up on the line after a marvellous jinking run.
Sale winger Chris Rhys Jones squandered a great chance in the corner following superb build-up play by the pack – and the hosts were left to rue their indecision as Quins closed out the game with a Staunton penalty with just two minutes left.
For Sale Sharks: Try: ToddCon: HaywardPens: Hayward 2
For NEC Harlequins:Tries: KeoghCon: Staunton Pen: Staunton 4