Topsy Ojo's second half try kept London Irish's slim top-four hopes alive and dented Harlequins' play-off chances.
The Heineken Cup semifinalists had failed to turn possession into points.
Quins took a 35th minute lead as Bristolbound Adrian Jarvis converted a penalty.
But Eoghan Hickey replied with two penalties midway through the second half before Ojo's 76th-minute try.
Irish captain Bob Casey was sin-binned from the resulting kick-off for obstruction and Jarvis kicked his second penalty.
Quins director of rugby Dean Richards said: "I think London Irish deserved to win on the day."
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JONATHAN PEARCE
ALEC STEWART
THE MOLE