Northampton booked themselves a home semi-final against Saracens after recording a 31-7 win over London Irish at the Madejski Stadium on Saturday.
Saints, who finished the regular season in second place, took an 11-0 lead into the break thanks to centre Jon Clarke's 39th-minute try and two penalties by Stephen Myler.
Chris Ashton, playing in front of watching England manager Martin Johnson and his fellow national team coaches, dotted down for Northampton's second try while Clarke added a third late on, with Myler kicking the rest of their points.
It was hardly the ideal way for 2003 World Cup-winning centre Mike Catt, playing the final match of his illustrious career, to bow out but he at least came off the bench for the last 13 minutes for a cameo appearance for Irish, for whom he will continue to be attack coach.
The hosts' only points came from Danie Coetzee's 65th-minute try, converted by Tom Homer, as Toby Booth's men ended the season in sixth place and with a lacklustre performance under their belts.
England full-back Delon Armitage was a late withdrawal from Irish's starting XV, and was replaced by winger Topsy Ojo, with Homer reverting to number 15.
Injuries have hit the Exiles hard this campaign, a key reason why one of the hot pre-season tips for the title have fallen short of a top-four finish thanks with just three wins in 2010, but they at least welcomed back star winger Sailosi Tagicakibau for the first time since February.
And the Samoa international enlivened the crowd on a chilly day in Reading with the first real break, sprinting 60 yards before being hauled down by opposite wing Ashton, who struggled against Tagicakibau in the first half.
Homer missed an angled, fourth-minute penalty attempt before Myler opened his account with a 35-yard kick after 18 minutes for 3-0.
Although defences were largely on top, Saints looked more dangerous out wide and they butchered a clear four-on-one overlap in the 25th minute after picking up turnover ball.
Myler extended the lead to 6-0 with a 35th-minute penalty and Northampton scored a killer try seconds before the break, Ashton sending away Clarke down the left wing for the centre to scamper over for his eighth of the season.
Myler missed the conversion and then a penalty chance early in the second half but the match was as good as won when Ashton went over in the 48th minute.
A quick tap fooled the Irish defence and after Soane Tonga'uiha had taken the ball on, Reihana laid a try on a plate for Ashton, who grounded under the posts for his 23rd of the season to allow Myler a simple conversion.
The fly-half kicked his third successful penalty of the afternoon for 21-0 as an increasingly bedraggled home side continued to come off second best in the tight.
Exiles supporters finally had reason to cheer in the 65th minute when, after a series of close-quarter attacking phases, Coetzee barged over from a yard with his team's first points of the match.
Homer added the extras before Catt entered the fray, to rapturous applause.
Saints saw full-back Ben Foden helped off the pitch at the same time, to be replaced by Shane Geraghty, and the England international was immediately given treatment by Saints medical staff.
Catt, 38, did not have any time to turn the tide in Irish's favour - although he was jokingly given the official man-of-the-match award - and Clarke had the last laugh with a late try down the left.
For London Irish:
Tries: Clarke 2, Ashton
Con: Myler 2
Pen: Myler 4
London Irish: 15 Delon Armitage, 14 Tom Homer, 13 Jonathan Joseph, 12 Elvis Seveali'i, 11 Sailosi Tagicakibau, 10 Ryan Lamb, 9 Paul Hodgson (capt), 8 Chris Hala'Ufia, 7 Steffon Armitage, 6 Richard Thorpe, 5 Matt Garvey, 4 Kieran Roche, 3 Faan Rautenbach, 2 Danie Coetzee, 1 Alex Corbisiero.
Replacements: 16 Rob Herring, 17 Dan Murphy, 18 James Tideswell, 19 Andy Perry, 20 Jamie Gibson, 21 Topsy Ojo, 22 Mike Catt, 23 Jamie Lennard.
Northampton: 15 Ben Foden, 14 Chris Ashton, 13 Jon Clarke, 12 James Downey, 11 Bruce Reihana, 10 Stephen Myler, 9 Lee Dickson, 8 Roger Wilson, 7 Neil Best, 6 Phil Dowson, 5 Juandre Kruger, 4 Ignacio Fernandez Lobbe, 3 Euan Murray, 2 Dylan Hartley (capt), 1 Soane Tonga'uiha.
Replacements: 16 Brett Sharman, 17 Regardt Dreyer, 18 Brian Mujati, 19 Courtney Lawes, 20 Mark Easter, 21 Alan Dickens, 22 Shane Geraghty, 23 Joe Ansbro.