Brian Smith’s Exiles fought back from 20-6 down at the break but ultimately came up short against Quins in front of a 60,000-plus crowd.
Irish found themselves well behind in the Aviva Premiership opener after tries from Ugo Monye and Ollie Lindsay-Hague, plus two conversions and penalties from Nick Evans, saw Quins put clear distance between themselves and the Exiles.
But Shane Geraghty kicked two first-half penalties and then set up a thrilling finish with three more in the second period to narrow the deficit to 15-20.
However, Smith’s men failed to find the winning score they needed in the closing stages as Quins held on.
London Irish did pick up a losing bonus point for their efforts and director of rugby Brian Smith said: “We couldn’t get going in the first 20 minutes and they rattled up the scores. We had got to half-time without firing any shots.
“We were outplayed in the first half but we reassessed at the interval and ultimately had a shot to win it.
“They are a quality outfit, so at half-time I would certainly have taken a bonus point.”
Irish will be looking to chalk up their first win of the Aviva Premiership season when they travel to Newcastle Falcons this Sunday (3pm).
London Irish: Homer; Ojo, Mulchrone, Sheridan, Short; Geraghty, Steele; Court, Paice, Aulika; Skivington (capt), Leo; Cowan, Treviranus, Guest. Reps: Ellis, Parr, Halavatau, Low, Gilsenan, O'Leary, Noakes, Fowlie.
Harlequins: Brown; Yarde, Hopper, Turner-Hall, Monye; Evans, Care; Marler (capt), Gray, Sinckler; Matthews, Robson; Wallace, Robshaw, Easter. Reps: Buchanan, Lambert, Collier, Merrick, Clifford, Dickson, Botica, Lindsay-Hague.
Attendance: 61,424.
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