Steve Hanley plundered two late tries to send Sale nine points clear at the top of the Guinness Premiership in a high-octane encounter at the Madejski Stadium.
London Irish appeared to be heading for victory when captain Mike Catt, who had replaced the misfiring Riki Flutey as kicker, slotted two penalties to snatch a 19-18 lead.
But former England winger Hanley pounced in the 78th minute and injury time to snatch all four points for the Sharks, who are now in pole position to claim home advantage in the play-offs
Sale suffered a injury scare in the 51st minute when Mark Cueto was carried from the pitch after damaging his left leg while trying to gather a kick.
Cueto tripped over a small advertising triangle close to the touchline and fell awkwardly onto the hard surface surrounding the pitch.
The England winger was in considerable pain and Sale can ill-afford to lose him ahead of next Sunday’s Heineken Cup quarter-final against Biarritz.
Jason Robinson’s early exit with what appeared to be a hip injury compounded a miserable day for the Sharks on the injury front
But director of rugby Phillipe Saint Andre will be pleased with his side’s fighting spirit after they struck back after going behind three times.
Sailosi Tagicakibau, Riki Flutey and Delon Armitage ran in tries as Irish set the first half alight.
But the boot of England fly-half Charlie Hodgson kept Sale in touch with hooker Andy Titterell crossing shortly after half-time to improve their victory chances.
Hodgson, back in action after recovering from the hamstring injury which ruled him out of England’s 28-24 defeat by Ireland last weekend, slotted an early penalty to calm Sale’s nerves.
But a blunder from England prospect Magnus Lund allowed Irish to seize the initiative in the 15th minute, with Tagicakibau pouncing when the openside lost the ball in contact.
With no one patrolling the blindside Tagicakibau set off on a lightning run down the left touchline which swept him past a despairing tackle from the out-paced Robinson and over the line.
Robinson, struggling following an earlier collision with Tagicakibau, left the pitch shortly after with Chris Mayor coming on to plug the gap.
Hodgson landed a second penalty but Irish struck again in the 24th minute by rounding off waves of attacks close to Sale’s line by feeding Flutey who crashed over.
The Kiwi fly-half finished superbly after riding a tackle from Mark Cueto and stretching out to touch down, but then missed the conversion to leave him point-less from three shots at goal.
In contrast, Hodgson was keeping the scoreboard ticking over with his third penalty but the Exiles were happy to math the Lion’s boot with tries.
Their third was a sublime individual score from Armitage who kicked the ball past Cueto and outran the England winger and the covering Paul Hodgson before gathering up and diving over.
Flutey’s kicking nightmare continued as he fluffed the conversion and Hodgson slotted another three points on the stroke of half-time to rub salt into the wound.
Sale made a blistering start to the second half when Titterell was driven over by his pack with the television match official confirming the score and Hodgson converted.
Cueto limped off in the 51st minute following his tumble off the pitch and was replaced by Valentin Courrent, while moments later Mayor dropped a scoring pass.
Mike Catt had taken over the kicking duties, missing the first then slotting two in quick succession to give the Exiles a 19-18 lead.
But an unforced error by Flutey allowed Sale not edge back in front with the Irish number 10 dropping a simple pass and allowing Hodgson to punt upfield.
He made 50 yards until Catt covered to deal with the danger but the Sharks arrived in number and the ball was recycled and fed left where Hanley won the race for the line.
Charlie Hodgson missed the conversion – his first error all afternoon – and then Paul Hodgson missed a tackle on Hanley which allowed Sale to complete their victory.