Chris Boyd's side lost Fraser Dingwall, Teimana Harrison and Juarno Augustus to injury before the game, lifting the number of players unavailable to a massive 23.
Saints were still able to field a strong starting 15, but they found it difficult to find a way through a resilient Sharks defence.
The black, green and gold only had two James Grayson penalties to shout about in torrid conditions.
Time and again, Saints kicked the ball to the corner, only to be thwarted by Sale, and Grayson was off target with a couple of shots at goal.
AJ MacGinty made his opposite number pay, racking up 15 points of his own, while Saints were hit by an early try in both halves, as Akker van der Merwe and Marland Yarde cruised in for scores.
Saints couldn't scale the mountain, no matter how hard they tried, and they only had young backs on the bench to turn to.
Tom Litchfield and Josh Gillespie were both introduced during the second half as they were both named among the replacements at late notice due to the Dingwall and Harrison injuries.
And Jono Ross powered over late on to put the seal on the Sale win.
Saints had started well despite the team selection disruption, but after kicking to the corner they were beaten at the breakdown, with Sale winning a penalty to relieve the pressure.
However, the Sharks soon conceded a shot at goal, allowing Grayson to kick Saints ahead.
It wasn't long before Sale got up and running though as they found their way over far too easily from an attacking lineout, with hooker van der Merwe the beneficiary.
MacGinty converted superbly in windy conditions before Grayson missed a chance to respond from the tee at the other end, sending his penalty wide.
Saints were then submerged by the Sharks as the rain swept across the AJ Bell Stadium, but some defiant defending and a scrum penalty gave the away side some welcome respite.
But Sale extended their lead with a MacGinty penalty on 28 minutes, and the fly-half was on target again four minutes later as the penalties started to stack up for Saints.
However, Sale weren't having it all their own way and Saints delivered a period of sustained pressure just before the break, resulting in an easy three points for Grayson.
Saints were well in touch at 13-6 down at half-time, but it felt like the next score would be crucial.
Sale got it just two minutes into the second half as a clever MacGinty kick found Yarde in acres of space out wide, and he cruised in for the try.
MacGinty kicked the conversion and at 20-6 down, it was looking like a long way back for Saints.
The away side were still able to win penalties in the Sale half, but there was just no way through from a series of attacking lineouts.
Frustration was growing for Saints as Sale continued to ship penalties and escaped without a yellow card.
Saints eventually decided to take a shot at goal from in front of the posts, but the anguish was amplified as Grayson missed.
MacGinty again made Saints pay as he slotted another penalty with 16 minutes to go.
There was plenty of huff and puff to follow as both teams went to their benches to try to freshen things up.
And Sale put the finishing touches to their win from the final play as Ross powered over, with MacGinty again adding the extras in fine fashion.
Sale Sharks: Hammersley; McGuigan, S James, van Rensburg, Yarde; MacGinty, Warr (Thomas 78); Rodd (McIntyre 50), van der Merwe (Langdon 56), Oosthuizen (Jones 64); JL du Preez, JP du Preez (Postlethwaite 72); Ross (c), B Curry (Dugdale 72), D du Preez.
Saints: Freeman; Skosan, Francis (Litchfield 66), Hutchinson, Collins (Gillespie 64); Grayson, James (Tupai 69); Waller (Iyogun 60), Fish (Haywood 56), Hill (Painter 56); Ribbans, Moon (Nansen 62); Coles, Wilkins, Ludlam (c).
Referee: Anthony Woodthorpe