The Exiles moved up to seventh in the standings after a narrow 22-19 victory at Twickenham Stoop.
For Quins, it was a missed opportunity to catch up on leaders Leicester as they fell to a third loss of the campaign, despite young winger Oscar Beard scoring his first two senior tries.
The London Irish took the first points of the game thanks to a simple penalty from Paddy Jackson after five minutes, while Quins failed to escape in a ruck.
A few forward passes made it difficult for the hosts to retaliate quickly, while a move involving Andre Esterhuizen and Danny Care, following Tommy Allan’s chip, broke down on the left.
But the Harlequins had their first try in the 23rd minute when Care’s hopeful kick to the left corner was not dealt by Tom Parton and Beard pounced on the loose ball to score.
Allan added the away conversion, but the Exiles hit back just before the half hour mark when Argentina hooker Agustin Creevy hit the ball from the back of a maul at the wheel, after a series of penalties.
Jackson’s conversion gave the visitors the advantage 10-7, but it took just seven more minutes for the lead to change hands again.
It also came from a delicious move, as Care sent Jack Walker through a gap in the middle and the hooker produced a nice discharge to put Luke Northmore in the free space to score under the posts.
It gave the Harlequins a 14-10 lead at halftime and it took a superb tackle from Jackson to stop Tyrone Green from passing and extending that lead eight minutes after the break.
His intervention then allowed the Exiles to regain the advantage, after a dangerous break from Parton, as Curtis Rona found former Australian lock Rob Simmons in space to go through to the right.
Jackson missing the conversion meant just one point separated the teams, but Irish managed more than a clear convert try when substitute scrum-half White made his way just before the hour mark.
Quins missed a great opportunity to quickly pull out a try when Jack Kenningham struck near the line after Beard brilliantly managed to gain some ground on the left.
Beard had his second with 13 minutes left when he entered the corner after Care and Tom Lawday combined to find him in space, but Quins couldn’t snatch a late winner this time around as the Irish stubbornly held on.
PA Supplementary Reports