A late try from replacement Sam Egerton wasn't enough for Harlequins as Sale triumphed 29-23 in the Premiership at AJ Bell Stadium on Saturday.
Quins picked up a losing bonus point, with a late converted try, moving above their opponents on points difference into fifth place.
Sale were last beaten at home in the Premiership by this weekend's opponents nearly a year ago, but lightning did not strike twice, despite a lacklustre first half from the home team.
Danny Cipriani, starting on the bench after wayward kicking in the 36-36 draw with Saracens last time out, proved crucial to the victory, kicking well following his introduction to the game.
The opening exchanges saw the two sides trading penalties, Harlequins' Ben Botica's effort sandwiched between two successful kicks from Joe Ford for the hosts.
Both teams played on the offence, and that meant either side looked likely to add to their tallies, but it was Ford again who did the duty from the tee to extend Sale's lead.
The gap was cut to three once more with Botica sailing an effort through the posts late on in the first half, before Quins took the lead with game's first try.
Scotland winger Tim Visser raced to the line having been fed the ball by Botica, who converted to make it 13-9.
Following an unusually disappointing first half from the home side, they came out fired up for the second, and TJ Ioane crossed the whitewash after great work in the driving maul.
Ford converted and Sale had a three point advantage. Botica then levelled the scores with another penalty, but Sale took command of the tie in the final 20 minutes as first, Ford's replacement Cipriani kicked home three points, before Will Addison touched down after a great team move involving Cipriani and Peter Stringer.
Sam James played in Addison before Cipriani converted for a 10 point advantage. With time running out, Cipriani kicked three more points to all but secure the points for Sharks.
However, Quins brought themselves to within a converted score of winning the game with the last action of the match. Samson Egerton drove over the line, with Botica converting, but it was too-little-too-late.
Tries: Ioane, Addison,
Cons: Ford, Cipriani
Pens: Ford 3, Cipriani 2
Tries: Visser, Egerton
Cons: Botica 2
Pens: Botica 3
Sale: 15 Mike Haley, 14 Will Addison, 13 Sam James, 12 Johnny Leota, 11 Tom Arscott, 10 Joe Ford, 9 Chris Cusiter, 8 Mark Easter, 7 David Seymour (c), 6 TJ Ioane, 5 Andrei Ostirkov, 4 Bryn Evans, 3 Brian Mujati, 2 Neil Briggs, 1 Eifion Lewis-Roberts
Replacements: 16 Tommy Taylor, 17 Ross Harrison, 18 Vadim Cobilas, 19 Jonathan Mills, 20 Cameron Neild, 21 Peter Stringer, 22 Danny Cipriani, 23 Mark Jennings
Harlequins: 15 Ross Chisholm, 14 Marland Yarde, 13 Matt Hopper, 12 Harry Sloan, 11 Tim Visser, 10 Ben Botica, 9 Tito Tebaldi, 8 Nick Easter, 7 Luke Wallace, 6 Mat Luamanu, 5 James Horwill (c), 4 George Merrick, 3 Kyle Sinckler, 2 Dave Ward, 1 Mark Lambert
Replacements: 16 Rob Buchanan, 17 Owen Evans, 18 Will Collier, 19 Charlie Matthews, 20 James Chisholm, 21 Sam Egerton, 22 Joe Marchant, 23 Charlie Walker
Referee: Ian Tempest
Assistant Referees: Ross Campbell, Steve Lee
TMO: Trevor Fisher