On rolled the replacements, with quickfire tries by Toby Flood and Ollie Phillips leaving the visitors just one score away from a bonus point and in the ascendancy.
It was not to be, however, with two Shane Geraghty tries against the run of play right at the death putting the Exiles beyond reach as Newcastle paid for their first half horror show.
As early as five minutes in the Irish were ahead through the boot of Geraghty, who struck a penalty before missing a further two.
The all-star Falcons back line, playing together for the first time, failed to fire on all cylinders as Geraghty, Catt and Mapusua probed effectively - Steffon Armitage dominating the breakdown to provide their platform.
Prop Tonga Lea'aetoa was the unlikely scorer of the opening try as he exploited Newcastle's decision to commit bodies to the ruck by going in on the overlap down the right hand side.
Starved of territory and possession, the Falcons' cause was done no favours by Joe McDonnell's dismissal to the sin bin for striking an opponent.
The damage was immediate as hooker Robbie Russell rumbled over for a textbook rolling maul score, both tries being converted by Geraghty.
There was more woe to come for a Newcastle team at sixes and sevens, as burly centre Mapusua burst through a tackle to score down the left hand side.
Newcastle's only real inroads to the home defence in the opening half did not come until the very end, repeated Irish infringements at close range rolling mauls not tempting referee Ashley Rowden to wield the yellow card as the hosts eventually cleared the pressure for a 24-0 interval lead.
A half-time rollocking and a raft of early replacements saw the visitors finally find their stride, dominating much of the final 40 as they exploited the fragmented game and open spaces.
Scrum half Lee Dickson, fullback Loki Crichton, flanker Brent Wilson and wing Ollie Phillips all made their presence felt as Newcastle attacked from deep and carved holes in a hitherto unbreachable home midfield.
With Dickson driving the pace the visitors finally found some front foot ball to work with, Flood's dancing feet seeing him past a string of opponents and linking well with supporting runners.
With mounting pressure on the London Irish line hooker David Paice was forced in to rash action with a high shot on Tom May, earning him ten minutes in the bin.
Just as London Irish had done, the Falcons exploited the extra man almost straightaway as Dickson and Crichton started a length-of-the-field move from counter-attack ball in their own 22. Good back-up play from Wilson saw the ball find the hands of Flood, with the England man stepping his way to the try line for a sensational team score.
Wilkinson added the extras, and the second try was not long in coming as Newcastle upped the pace and utilised the open field to good effect.
Having pushed play in to the home 22 they pinched a timely line out through Russell Winter at the back, the resulting move seeing Phillips switch flanks to hit a perfect line down the left wing and score in the corner.
The missed touchline conversion left the Falcons still five short of a bonus point, but with wave after wave of attack it seemed only a matter of time before the crucial score woulld come.
With Crichton and Flood driving the creative tempo the forward runners started to hit some hard straight lines, Parling and Sorenson smashing in to the home defence while Wilkinson was just metres short of a score down the right.
With so many men committed in attack, however, there was to be a major sucker punch as the hosts turned late possession in to two tries from Geraghty, both mirror images of each other as he gave a show-and-go on the 22 before cantering under the posts.
Wilkinson departed with cramp as the final seconds ebbed away, and the Falcons were made to pay for their earlier lapses.
London Irish:
Tries: Lea'aetoa, Mapusua, Russell, Geraghty 2
Cons: Geraghty 5
Pens: Geraghty
Newcastle Falcons:
Tries: Flood, Phillips
Cons: Wilkinson
London Irish:
15 Riki Flutey
14 Delon Armitage
13 Seilala Mapusua
12 Mike Catt (captain, Topsy Ojo, 76)
11 Sailosi Tagicakibau
10 Shane Geraghty
9 Paul Hodgson (Ben Willis, 77)
1 Neal Hatley
2 Robbie Russell (David Paice, 38)
3 Tonga Lea'aetoa (Michael Collins, 51)
4 Nick Kennedy
5 Bob Casey (James Hudson, 65)
6 Kieran Roche (Olivier Magne, 61)
7 Steffon Armitage
8 Phil Murphy (Juan Leguizamon, 65)
Newcastle Falcons:
15 Matthew Burke (captain, Loki Crichton, 53)
14 Tom May (Ollie Phillips, 60)
13 Mathew Tait
12 Jamie Noon
11 Toby Flood
10 Jonny Wilkinson (Jason Oskes, 74)
9 James Grindal (Lee Dickson, 45)
1 Joe McDonnell
2 Matt Thompson (Andy Long, 53)
3 Micky Ward (Jon Golding, 53)
4 Mark Sorenson
5 Jason Oakes (Andy Buist, 60)
6 Geoff Parling
7 Cory Harris (Brent Wilson, 45
8 Russell Winter
Referee: Ashley Rowden
Attendance: 10,003
