London Welsh led for much of the first half but a quickfire treble of tries just after the hour secured victory for Irish.
Gordon Ross's seventh-minute penalty put the visitors in front, but their lead was short-lived, as Irish found an instant response to hit the front, when Guy Armitage muscled his way over the line following good work at the line-out.
Ian Humphreys' conversion made it 7-3, though the plucky visitors remained in the contest through Seb Stegmann's unconverted try.
A flurry of points before the second half saw Irish's lead extended, with Halani Aulika and Chris Hala'ufia crossing for a quickfire brace of tries after Welsh head taken the lead through Nick Scott's well-worked try.
There were plenty more points in the second half, and Irish wasted little time in extending their lead, as Aulika crossed for his second try for Humphreys to convert.
Welsh remained in the contest through two quickfire Ross penalties, but three home tries in ten minutes just after the hour killed the game as a contest.
Sailosi Tagicakibau got the ball rolling on 61 minutes, before Matt Garvey crossed and Armitage got his second.
Humphreys converted all three tries to make it 47-21, though Welsh's efforts throughout the contest were rewarded with the final points of the game.
Greg Bateman's well-worked try was converted by Ross, and though the visitors were well beaten, they emerged from the contest with their head held high, despite having been condemned to relegation a week earlier.
For London Irish:
Tries: Armitage 2, 'Aulika 2, Hala'ufia, Tagicakibau, Garvey
Cons: Humphreys 6
For London Welsh:
Tries: Stegmann, Scott, Bateman
Pens: Ross 3
London Irish: 15 Tom Homer, 14 Marland Yarde, 13 Guy Armitage, 12 Steven Shingler, 11 Sailosi Tagicakibau, 10 Ian Humphreys, 9 Darren Allinson, 8 Chris Hala'ufia, 7 Ofisa Treviranus, 6 Matt Garvey, 5 Bryn Evans, 4 George Skivington (capt), 3 Halani Aulika, 2 David Paice, 1 Alex Corbisiero.
Replacements: 16 Scott Lawson, 17 Jerry Yanuyanutawa, 18 Leo Halavatau, 19 Kieran Low, 20 Declan Danaher, 21 Topsy Ojo, 22 Shane Geraghty, 23 Jack Moates.
London Welsh: 15 Tom Arscott, 14 Nick Scott, 13 Seb Stegmann, 12 Sonny Parker, 11 Dan Caprice, 10 Gordon Ross (capt), 9 Tyson Keats, 8 Daniel Browne, 7 Michael Hills, 6 Julio Cabello Farias, 5 Kirill Kulemin, 4 Matt Corker, 3 Paulica Ion, 2 Greg Bateman, 1 Tom Bristow.
Replacements: 16 Dan George, 17 Arthur Joly, 18 James Tideswell, 19 Adam Brown, 20 Adam Balding, 21 Rob Lewis, 22 Alex Davies, 23 Joe Ajuwa.
Venue: Madejski Stadium
Referee: Dean Richards
Assistant referees: Gareth Copsey, Nigel Carrick