England's Marcus Smith led the way with a 24-point individual haul as 2021 Premiership champions Harlequins ended Sale's unbeaten start to the season.
Smith converted his own try for the second of his side's two first-half scores, having added to the opening try by Nick David, as well as going on to kick five penalties.
Sale briefly led when Sam James' try was followed by two Rob du Preez kicks.
But, having led 17-10 at the break, Quins then outkicked their hosts.
Sale's hopes of starting the season with a sixth straight Premiership win were ended by a dominant performance backed up by Smith's boot, as he kicked four second-half penalties to just one more from du Preez, as Quins earned only their third win of the campaign.
More to follow.
Sale: Carpenter; Roebuck, S James, Tuilagi, O'Flaherty; R du Preez, Quirke; Rodd, Ashman, Schonert, Wiese, J Hill, Ross, T Curry, D du Preez.
Replacements: Taylor, McIntyre, Harper, Beaumont, du Preez, Warr, S Hill, Reed.
Harlequins: Allan; David, Marchant, Esterhuizen, Murley; M Smith, Care, Marler, Musk, Louw, Lamb, Herbst, Kenningham, Evans, White.
Replacements: Riley, Garcia Botta, Kerrod, Hammond, Jurevicius, Gjaltema, Edwards, Anyanwu.
Referee: Christophe Ridley (RFU)
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