In what was a repeat of last season's final, Sale's 20-10 victory on Saturday's last day of the regular campaign came despite Tuilagi, celebrating his 33rd birthday, being forced off with a hamstring injury after 17 minutes.
Initial indications were that the powerhouse England centre's season had come to an end and that he would miss the semi-final against Bath on June 1 and a possible Twickenham final before his move to French club Bayonne.
Saracens' defeat condemned them to a last-four clash away to Northampton on May 31 after they had been favourites for a home tie.
It also meant Saracens star Owen Farrell had played his last home game for the London club ahead of the former England captain's post-season move to Paris-based Racing 92.
Northampton and Saracens had already secured play-off spots before Saturday's final round of regular season games, with five other clubs vying for the two remaining places.
But Sale's win meant all the teams that kicked off in the top four remained in the play-off places, albeit that Saracens' defeat dropped them from second to fourth place, with Bath finishing next in line behind table-toppers Northampton.
Saracens suffered a setback before kick-off when Scotland wing Sean Maitland, who had announced Friday he would be retiring at the end of the season, suffered a freak injury in the warm-up and had to pull out.
Sale were expertly led by England fly-half George Ford as tries from Tom Roebuck and Rob Du Preez established a 20-3 lead with 30 minutes left.
Saracens threatened a fightback when Marco Riccioni went over to make it a 10-point game.
But Sale held firm as they enjoyed a first away league win over Saracens since September 2005.
Bath secured their play-off place by scoring six tries in a 43-12 rout of Northampton.
Bristol overwhelmed Harlequins 58-23 and Leicester defeated Exeter 40-22 but results elsewhere denied the Bears and the Tigers a play-off spot.
At the other end of the table, Newcastle ended the Premiership season without a single win following a 54-14 loss at home to Gloucester.
Defeat meant Newcastle followed Rotherham (2003/04) and London Welsh (2014/15) in failing to post a solitary league win in a season, with Saturday's reverse leaving the Falcons with a mere five points from their 18 league fixtures.
Newcastle's owners deliberately reduced their spending on players after three other Premiership clubs —- Worcester, Wasps and London Irish —- all went bust last season.
With no realistic prospect of relegation they relied on a young and inexperienced squad, with the northeast club prepared to suffer short-term pain in the hope of avoiding the example of the three clubs that no longer exist.
For Gloucester, who suffered a humiliating 90-0 defeat by Northampton last time out, this was a morale-boosting win ahead of next week's European Challenge Cup final against South Africa's Sharks.
