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The hosts scored six tries, including four for Irishman Shane Monahan, to claim the five points.
London Irish dominated the opening quarter but only had a Tom Homer penalty for their efforts. The Exiles deprived Gloucester of ball but Freddie Burns kicked two penalties to put the hosts in front.
The Cherry and Whites sprang into action on half an hour. Jimmy Cowan put Shane Monahan into a hole and the big Irishman broke through the tackle and went on an arching run to finish in the corner. Freddie Burns kicked the conversion to make it 13-3 to Gloucester.
Two minutes before half time Freddie Burns kicked his third penalty before Monahan crossed for his second on the stroke of half time to give Gloucester 23 points to 3 lead at the break.
Shane Monahan added two second half tries to confirm the victory and cap a personal man of the match performance.
Rob Cook scored a try three minutes into the second half and Dan Robson came on to score a fantastic individual try six minutes from time to make the final score Gloucester 47 London Irish 3.
The Exiles host Leicester Tigers at Madejski Stadium next weekend in a crucial Aviva Premiership encounter.
Score sequence (London Irish first): 0-3, 3-3, 3-6, 3-13, 3-16, 3-23, 3-30, 3-37, 3-42, 3-47
Scorers: Gloucester: Penalties: Burns (6, 24, 38); Tries: Monahan (35, 39, 59, 71), Cook (44), Robson (74); Conversions: Burns (4); London Irish: Penalties: Homer (12)
15. Rob Cook (rep Martyn Thomas, 65); 14. Charlie Sharples; 13. Mike Tindall (rep: Tim Molenaar, 60); 12. Billy Twelvetrees; 11. Shane Monahan; 10. Freddie Burns; 9. Jimmy Cowan (rep: Dan Robson, 53); 1. Dan Murphy (rep: Nick Wood, 50); 2. Darren Dawidiuk (rep: Koree Britton, 50); 3. Rupert Harden (rep: Shaun Knight, 19); 4. Will James; 5. Jim Hamilton (Captain); 6. Tom Savage (rep: Matt Cox, 60); 7. Akupusi Qera; 8. Sione Kalamafoni (rep: Gareth Evans, 60)
Replacements: 16. Korre Britton; 17. Nick Wood; 18. Shaun Knight; 19. Matt Cox; 20. Gareth Evans; 21. Dan Robson; 22. Tim Molenaar; 23. Martyn Thomas
London Irish team
15. Tom Homer; 14. Topsy Ojo (rep: Conor Gaston, 65); 13. Steven Shingler (rep: Declan Danaher, 74); 12. Guy Armitage; 11. Anthony Watson (rep: Sailosi Tagicakibau, 60); 10. Shane Geraghty; 9. Darren Allinson (rep: Jack Moates, 52); 1. Max Lahiff (rep: Jerry Yanuyanutawa, 40); 2. David Paice (rep: Scott Lawson, 40); 3. Halani Aulika (rep: Leo Halavatau, 40); 4. James Sandford (rep: Matt Garvey, 53); 5. Bryn Evans (Captain); 6. Kieran Low; 7.Jamie Gibson; 8. Alex Gray
Replacements: 16. Scott Lawson; 17.Jerry Yanuyanutawa; 18.Leo Halavatau; 19. Matt Garvey; 20. Declan Danaher; 21. Sailosi Tagicakibau; 22. Conor Gaston; 23. Jack Moates
Referee: Neil Paterson
Attendance: 10, 535