Winger Fenby, 30, a qualified chartered accountant, played for Newcastle and Scarlets before joining Irish in 2013.
Former Harlequins back-row Guest, 31, brings a 14-year playing career to a close having won the Premiership, European Challenge Cup and LV= Cup.
Injuries restricted him to just two Premiership starts this season, his second with London Irish.
Fenby scored two Premiership tries this term as well as a hat-trick against Edinburgh in the European Challenge Cup pool stage.
"I have really enjoyed my time with London Irish and it's with a heavy heart I've come to make this decision and pursue a new opportunity," he said.
Guest made more than 200 appearances for Quins and scored three times for the Exiles and admitted retirement was a tough decision to take.
"There are a lot of experiences that will live long in my memory, and I am grateful to have played rugby at the highest level for many years," he added.
London Irish players Andrew Fenby and Tom Guest have announced their retirement from professional rugby.