The 29-year-old ex-Scarlets captain, has left "by mutual agreement".
He played for Wales Under-21s and Wales Sevens before a senior call-up to tour New Zealand in 2010.
McCusker's Wales debut against South Africa in November that year and won his last cap in the 22-18 tour win over Japan in 2013.
He joined Scarlets in 2003 and went on to make 135 appearances, scoring six tries and led them in 2012-13 before being a joint captain with Jonathan Davies the following season.
McCusker said: "There have been some memorable experiences over the years including great Heineken Cup victories over Perpignan and Racing Metro and a big thank you must go out to the fans who support us through the highs and lows.
"It's been an honour to have played for such a fantastic club for so many years, but I'm looking forward to new challenges with London Irish."
Scarlets general manager of rugby Jon Daniels said: "At this stage in his career Rob understandably needs to be playing regular rugby, an opportunity which I am sure he will grasp with both hands at London Irish.
"On behalf of the Scarlets I would like to thank Rob for his contribution and wish him the very best for the future."
Six-times capped Wales back-rower Rob McCusker has left Scarlets to join Aviva Premiership side London Irish on a one-season deal.