Exiles ran in six tries in an impressive display of attacking rugby to overwhelm their opponents and finish seventh in the table.
Over 9,000 supporters flocked to the Madejski to say goodbye to the likes of Bob Casey, Delon Armitage, Kieran Roche, Nick Kennedy and Paul Hodgson.
And not only were the home fans treated to an enthralling performance from Exiles, but they again saw the wealth of talent that will still be at the club next season.
Jonathan Joseph, Saliosi Tagicakibau and Tom Homer were all instrumental in the victory, while Marland Yarde scored two tries after coming on as a replacement.
Homer, as he has been all season, was especially key for Irish, kicking 22 points to finish well clear at the top of the Premiership scoring charts.
The full-back converted four penalties in the opening 20 minutes in response to Freddie Burns' early three-pointer for Gloucester.
And although the visitors got the first try of the match through Tom Voyce, Homer responded with a fifth penalty to give Irish a 15-8 lead.
Armitage then set up Exiles' opening try, bursting free down the left wing and feeding in Darren Allinson to score.
Homer converted to extend Irish's advantage further, and even though Burns hit back with a penalty, the hosts blew Gloucester away with a couple of tries late in the half.
Tagicakibau scored the first from Allinson's pass before Joseph showed great speed to dart through the defence and race away to the line.
With Homer converting one of the tries, Irish went into the break with a healthy 34-11 lead.
Gloucester managed to stem the Irish flow at the start of the second half and both teams then had players dismissed after a huge melee broke out on the halfway line.
David Paice and Gloucester captain Jim Hamilton were the pair sent off for throwing punches, and it got worse for the visitors as they saw Mike Tindall yellow carded for an infringement not long afterwards.
Homer kicked the subsequent penalty before both he and Casey were withdrawn, the latter to a standing ovation.
Irish didn't let up, though, and replacement Yarde got on the scoresheet when he collected a neat kick over the top by Kieran Roche, who is retiring from rugby this summer.
Armitage then got a well-deserved try in his final appearance for the club before Joseph raced away and fed in Yarde to double his personal tally and take Exiles past the 50-point mark.
Voyce managed a late response for Gloucester but it didn't take any of the shine off a dominant victory for Irish.