Irish had already lost three times to their hosts in domestic and European competitions this season, but two first-half tries from lock George Skivington helped the Exiles exact revenge.
Centre Steven Shingler added a penalty and conversion, while England international Freddie Burns booted four Gloucester penalties, yet Irish deserved a first Premiership away victory this season at the seventh attempt, which was sealed by full-back Tom Homer's late penalty.
It took them five points above bottom club Sale Sharks, who tackle Saracens on Sunday, and sent them into a five-week league break with renewed optimism of avoiding the drop.
In contrast, a losing bonus point was scant consolation for Gloucester after a four-month unbeaten home record disappeared.
In the day's other game, Northampton climbed to fourth place as they became the first side to beat Exeter Chiefs at Sandy Park in the league this season.
Tries from Ken Pisi, Soane Tonga'uiha and Gerrit-Jan van Velze steered the visitors to a 30-19 victory, with Stephen Myler kicking three conversions and three penalties.