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.

Known as the Queen of Ranthambore, Machli was described as one of the world's most photographed tigers. She had distinctive fish-shaped markings on the left side of her face.
She featured in many documentaries and amazed viewers when her fight with a 14-foot crocodile was caught on film.
She was one of the biggest draws for thousands of tourists visiting Ranthambore National Park,
India has more than half the world's tigers, at 2,226 in the latest estimate.
Machli was found starving and lying on her side near the park's boundary in northern Rajasthan state. She had not eaten in days, officials said.
"We were trying to provide her treatment but she died," Ranthambore tiger project director Yogesh Kumar Sahu told AFP news agency.  "It was a natural death linked to her age."
Machli had slowed down in recent years and lost almost all of her teeth, according to the park's website.
Her death has made headlines in India, and fans have taken to social media to pay their respects to the Queen of Ranthambore.
She was named Machli, the Hindi word for fish, because of the markings on her face.
Natural World BBC photo credit: MACHLI - TIGER QUEEN/Natural World/Mike Birkhead Associates/BBC

The match, in Montevideo on Friday, 30 May, will be broadcast on the Red Button and also be streamed on the BBC Sport website. You can press the Red Button on either BBC One NI or BBC Two NI to watch the match.
Kick-off for the match at the Estadio Centenario is 00:30 BST and the commentator will be Michael McNamee.
Uruguay are in England's World Cup pool, Group D.
On Freeview and BT Vision, the Red Button feed can be found on Channel 301, on Freesat Channel 981 and Virgin Media Channel 991.
For those watching with Sky, coverage will be available only by pressing the Red Button.
Alternatively fans can also watch the game live by logging on to bbc.co.uk/sportni.
Shane Glynn, editor of BBC Sport NI, said: "Uruguay will be a tough test for Northern Ireland.
"They will be one of the sides who fancy their chances of winning the World Cup - and with players of the calibre of Luis Suarez and Edinson Cavani, why not?
"I'm delighted BBC Northern Ireland has secured the rights to show the Uruguay game live on the Red Button and via our BBC Sport NI website.
"We will also broadcast on the website an extended highlights package of the friendly match against Chile the following week."
Patrick Nelson, chief executive of the Irish Football Association, said: "We are delighted that BBC Northern Ireland have obtained the rights to show this game live on their Red Button and internet services. Northern Ireland fans all over the UK will be able to see live how well our team does against one of the World Cup favourites."
London Irish players Andrew Fenby and Tom Guest have announced their retirement from professional rugby.
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India's most famous tiger, 19-year-old Machli, has died, officials say.
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Northern Ireland's friendly against Uruguay is to be shown live on the BBC.