Saracens were going for a fifth successive league game without defeat, and the signs looked good when they led 9-0 at half-time – but four unanswered tries from the visitors put pay to their hopes.
Flanker Kieran Dawson's injury-time try secured a bonus point for the Exiles as they denied Saracens a chance of claiming fifth place following a recent resurgence under new head coach Steve Diamond.
Dawson's score, which came from the game's final move, rubbed dirt in Saracens' faces.
Everything looked rosy in the garden as they established a comfortable half-time advantage thanks to three penalties from fly-half Glen Jackson, but it all started to go wrong the minute Irish centre Rod Penney slashed through to score a try that Mark Mapletoft converted.
Even though Jackson put Saracens five points ahead with his fourth penalty shortly afterwards, the final 25 minutes belonged exclusively to Irish.
Scott Staniforth powered over after a bulldozing run by replacement Roland Reid with his first contribution, and then Reid's fellow substitute Ryan Strudwick claimed an interception try after Barry Everitt kicked two penalties in quick succession.
The victory will come as a huge relief to Irish coach Gary Gold, who has seen his team dragged towards the relegation area, but there was no doubting their supremacy during the second half.
Saracens' lingering hopes of reaching the Premiership play-offs have now effectively disappeared with just six games remaining and Diamond will be furious at the way in which Irish were allowed to dictate events after his team had done much of the hard work.
Having been given the cushion of three Jackson penalties, Saracens should have built on their advantage, but Irish established a territorial foothold and Saracens played almost the entire second period penned inside their own half.
Penney's score gave Irish hope that they could conjure up a win and, when Staniforth crashed over to tie the scores, Saracens desperately needed inspiration to get themselves going again.
Gold, though, expertly used his substitutes and Everitt arrived as a 60th-minute replacement for Mapletoft, he was quickly into the action, rifling over a penalty double.
Even as the game entered injury time, Saracens still had a losing bonus point within their grasp, but that was ridden away from them in dramatic fashion.
First of all, Strudwick made victory certain for Irish by galloping across for a try that Everitt improved and then Staniforth's searing touchline dash reaped the rewards it deserved when a supporting Dawson collected his pass to score.
The Irish bench was a scene of wild celebration, but Diamond's disconsolate expression told its own story and he must now pick up his players for a testing trip to Leeds in just five days' time.
"It is very disappointing – the first half was fair, but we did not come out of the changing rooms for the second period," said Diamond.
"One or two of our lot were suffering from some altitude sickness by looking at the league table, but we have been brought back to earth with a bump.
"We have done reasonably well since November, but when Irish got it back to 12-12, that was when they started asking more questions of us, and then is when you need leadership in your side.
"The pressure told, but to lose that like is not what we are after,"
For Saracens:Pens: Jackson 4
For London Irish:Tries: Penney, Skuse, Strudwick, DawsonCons: Mapletoft, EverittPens: Everitt 2