Saints suffered their first home defeat to Sale since May 2006 as they slumped to a 34-25 loss at Franklin's Gardens on Saturday afternoon.
Denny Solomona delivered a first-half hat-trick for the away side, with Marland Yarde also registering to make sure of the bonus point before the break.
Saints, who had won all four of their previous 2018 home fixtures, did rally during the second half, with Michael Paterson, Rob Horne and Heinrich Brüssow dotting down.
But it was nowhere near enough as Sale brought an end to a streak of nine successive Gardens defeats.
Saints staff and supporters had battled hard in the build-up to the game, working through the night to ensure the sub-zero temperatures and heavy snowfall did not spark a postponement.
But when the game started, they may have wished it had been called off as Sale started with real vigour.
A couple of handling errors early on presented the Sharks with possession inside the Saints half, with the away side threatening to score first.
And after Saints skipper Christian Day was forced off with an injury, Sale got their score, moving the ball to the right, where danger man Solomona found space to dot down.
De Klerk kicked the conversion to give his side a 7-0 lead after seven minutes, and Saints soon suffered another injury blow with Tom Wood hobbling off.
De Klerk added insult to injury with a fine penalty attempt from close to halfway, taking his team into a 10-0 lead.
Piers Francis spurned the chance to respond for Saints with a penalty of his own, hitting the upright from a position that looked extremely favourable.
But Francis soon made amends with another effort to put his team on the board.
Sale weren't deterred though and after Yarde did well to buy his team some space, a slick team move was finished by Solomona.
De Klerk made it 17-3 with the conversion and Saints had a mountain to climb after just 28 minutes.
Francis ate into the deficit with a penalty after Sale were put under real pressure in their own 22, but the Sharks had plenty of bite in attack, causing problems whenever they got into Saints territory.
And they were to score two more quickfire tries before the break.
First, Solomona was released by de Klerk to score his hat-trick try and then Yarde latched onto a kick from the South African scrum-half, booting the ball ahead and gathering to dot down.
De Klerk kicked both conversions, maintaining his 100 per cent record from the tee to make it 31-6 at the break, leaving Saints stunned.
But the home side were sent out with a flea in their ear and Paterson scored within two minutes of the restart.
Francis converted and flanker Jono Ross was sin-binned straight after as Sale failed to listen to warnings from referee Wayne Barnes, giving Saints extra hope of a stirring comeback.
But Luther Burrell and Brüssow continued an afternoon of injury woe, with both men forced off the field early in the second half.
Brüssow did manage to return from a head injury assessment with his team well on top, and Saints scored again after a fine long pass from Francis set up Horne on the right.
Francis missed the conversion, but Sale were losing their way and full-back Mike Haley was soon heading to the sin bin for deliberately tripping Horne.
De Klerk missed a penalty chance for Sale soon after, but then quickly made amends to make it 34-18.
Brüssow burrowed over to bag his first Saints try and Francis converted to cut the gap to nine points with as many minutes to go.
But Sale saw the game out to ensure they claimed a long-awaited Gardens success and left Saints and their supporters with nothing to show for their efforts.
Saints: Tuala (Pisi 65); Tuitavake, Horne, Burrell (Myler 43), Foden; Francis, Groom (Reinach 51); Ma'afu (van Wyk 61), Haywood, Brookes (Ford-Robinson 61); Ratuniyarawa, Day (c) (Paterson 4); Wood (Gibson 8), Brüssow, Harrison.
Sale Sharks: Haley; Solomona, Addison (c), L James, Yarde; S James, De Klerk (Cliff 65); Harrison, Webber, John (Aulika 71); Evans (Beaumont 65), Ostrikov; Ross, B Curry (Neild 42), Strauss.
Referee: Wayne Barnes