The loss leaves Quins staring into the abyss. There are now just five points seperating the bottom five clubs and Worcester – currently last – have a game in hand.
Before today, the Exiles had just a solitary victory to show from their last nine league matches – has owed much to their inability to cross the whitewash, but that was hardly a problem that affected them today.
Delon Armitage, Bob Casey and Roland Reid all touched down while the boot of Barry Everitt did the rest to secure Irish four crucial points in a tense but error-strewn clash at The Stoop.
Quins' former Wales fly-half Arwel Thomas kept his side in touch by slotting five penalties while Ugo Monye scored their only try, but they were deservedly edged by the free-scoring Exiles.
The race to escape relegation from the Premiership now looks set to go right down to the wire with Leeds' victory at Gloucester today making it impossibly tight with two matches remaining.
Will Greenwood, making his first start in four months after overcoming shoulder surgery, was given little opportunity to impress Lions boss Sir Clive Woodward who names his 44-strong squad for New Zealand on Monday.
The England centre came through unscathed but was a victim of Quins' lack of ambition during large spells of the match as they were reluctant to spread the ball wide, instead opting to smash their way up the middle whenever possible.
Irish showed greater ambition throughout and signalled their intent right from the start with Everitt slicing through the midfield only to then knock on while trying to find his support runner.
A raking touch-finder swept Quins deep into opposition territory and when Irish infringed in the face of heavy pressure Thomas was able to rifle over a penalty which drifted off and then on target in the blustery conditions.
The Exiles replied with a simple three points from Everitt after Geoff Appleford and Michael Horak had gone desperately close to crossing with Quins' defence stepping off-side.
Irish won two more penalties as the home side struggled to wrestle free of their opponents' grip but they opted to go for the line-out and then scrum with both set-pieces amounting to little.
A try seemed inevitable, however, and it arrived in the 27th minute when a break from Appleford set up a chance for Armitage who showed some impressive finishing skills to cross in the corner.
Everitt landed the conversion before Thomas slashed the deficit with his second penalty as a dismal first half – both sides had committed a host of errors – neared its eagerly awaited conclusion.
Quins finished with a flourish though, moving into an advanced position after some effective interplay between Ace Tiatia and Jim Evans at a line-out, and were rewarded when Thomas booted three more points.
The little Welshman nudged Quins into the lead shortly after the restart but Irish threatened to restore their advantage when Mike Catt went racing through after linking nicely with Everitt.
He only had full-back Gavin Duffy to beat but his chip over the top was too strong and Quins were able to break free with a surging run from Greenwood.
But the Exiles could not be denied in the 52nd minute when winger Scott Staniforth set off on a weaving run which took him past Duffy and just as he had run out of space, lock Casey was on hand to finish off the move.
Everitt added the conversion but the score was levelled 17-17 five minutes later when Daffyd James used his strength to create an opening down the left and he stood up well in the final tackle to supply the scoring pass to Monye.
A costly blunder from scrum-half Steve So'oalo saw Irish regain the initiative as he obstructed Horak who had chipped through, earning 10 minutes in the sin-bin and handing Everitt three points on a plate.
Quins drew level with a Thomas penalty but the Exiles stormed back in front when number eight Reid took advantage of sloppy defence to crash over for the winning score.
For NEC Harlequins:Try: Monye Pens: Thomas 5
For London Irish:Tries: Armitage, Casey, Reid Cons: Everitt 2Pens: Everitt 2