Barry Everitt was the Irish hero, casually slotting a penalty three minutes into added time after Charlie Hodgson had looked to have won it for the home side.
Sale started the game at a whirlwind pace and continued their habit of scoring early when Sebastien Bruno went over after just three minutes.
England international Chris Jones stole a London Irish line-out and scrum-half Bryan Redpath launched a box kick which Delon Armitage failed to gather.
Jones collected and carried the ball into the Irish 22 before feeding the ball inside to the supporting hooker who outstripped the Irish support and dived over in the corner. Hodgson converted from the touchline.
Everitt got Irish on the scoreboard three minutes later when he slotted a 40-metre penalty after Sale were caught offside in the midfield.
Everitt was on target again on 14 minutes after referee Steve Leashing penalised Robert Todd for killing the ball.
Hodgson made the score 10-6 when he kicked a 30m penalty after the Irish were offside at the breakdown.
Irish struck back after 32 minutes when Armitage showed a devastating turn of pace to get the better of some illustrious would-be tacklers.
The Irish move looked to be going nowhere with some laboured passing in the midfield, until Armitage got the ball 30m from the line.
The late replacement for the injured Scott Staniforth slipped through the tackles of Steve Hanley and Jason Robinson to crash over in the corner.
Everitt narrowly missed the conversion, but Irish still turned round 11-10 in front.
Irish were rewarded for some persistent pressure after 57 minutes when Sale were again caught offside at the breakdown. Everitt knocked over the kick to make the score 14-10 to Irish.
Hodgson kicked another penalty on 69 minutes to make the score 14-13 to the visitors.
The game took a remarkable twist with just two minutes of normal time to play.
Robert Todd made a bullocking run into the Irish 22 and the ball was recycled quickly.
Replacement Mike Hercus tried to float a pass over the Irish defence but Irish winger Justin Bishop intercepted and sped 40 metres up the pitch before being tackled by Robinson.
Steve Leashing penalised Bishop for holding onto the ball and Hodgson looked to have won the game when he slotted the penalty.
The Irish responded magnificently and forced their way back into the Sale half.
The ball went through several phases of play before Jason White was penalised for a blatant offside. Everitt slotted the kick to ensure a famous Irish win.
For Sale Sharks:Try: BrunoCon: HodgsonPens: Hodgson 3
For London Irish:Try: ArmitagePens: Everitt 4