AJ MacGinty's late penalty ended Sale Sharks' run of 10 consecutive defeats as they overcame the Scarlets 25-23 at the AJ Bell Stadium.
Sale started the match outstandingly and opened up a 16-0 advantage after 28 minutes through Paolo Odogwu and Will Addison tries, while AJ MacGinty kicked two penalties.
The Welsh region were slack in that opening half hour but improved late on in the first period and reduced the deficit via Dan Jones' three-pointer and DTH van der Merwe's converted touchdown.
Two MacGinty penalties to Jones' one gave the Sharks a 22-13 advantage going into the final quarter-final but a penalty try for the Pro12 side set up an exciting finale.
Jones did take the Scarlets ahead but MacGinty sealed the win late on from the tee.
The Manchester outfit have found it tough in Europe's top-tier over recent years, succumbing to 16 consecutive defeats before this encounter, but started brightly.
Steve Diamond's men were physical and abrasive, forcing the visitors into mistakes, and an infringement at the contact area allowed MacGinty to have a shot at goal, which he duly converted.
Minutes later, Aled Thomas burst through a hole for Wayne Pivac's side but they were soon back under pressure.
Sale then went through the phases and, after the forwards had sucked in the Scarlets' defenders, Addison freed Odogwu to score.
Another Scarlets error gave MacGinty a second three-point chance. Once more he found the target and Sale moved 11-0 in front. Sharks had the momentum and they went further ahead thanks to a piece of individual brilliance by their captain Addison, who took the ball on halfway, scythed through the opposition rearguard and crossed the whitewash.
The Llanelli-based outfit were now 16 points in arrears but, with half-time looming, they managed to forge a way back into the contest. Firstly, Jones was successful off the tee before Aaron Shingler sprinted down the right wing, drew the final defender and sent van der Merwe scampering over on the stroke of half-time.
MacGinty and Jones traded penalties just after the break but it was the hosts that were creating the majority of the opportunities with Addison particularly impressing. When he and centre partner Mark Jennings combined, the visitors were forced to infringe and MacGinty extended their buffer. However, the Scarlets were not finished and they pressurised the Sharks via their maul.
When one such drive took them to within inches of line, Magnus Lund illegally pulled it down, earning him a yellow card and giving referee Pascal Gauzere no other option than to award a penalty try.
Down to 14 men, the home side were now on the back foot and the visitors took the lead for the first time in the match through Jones' three-pointer. But the Manchester outfit had the final word when MacGinty kicked them to a much-needed win.