He scored 72 points in the Heineken Cup last season to help guide Ulster into quarter-finals for the first time in 12 years.
He was again influential in this season's European campaign, scoring all of the province's points in their 16-11 home win over French giants Clermont Auvergne.
The 30-year-old was among the replacements as Ulster beat Edinburgh in the semi-final last weekend to book a place in their second ever European Cup final, to be played at Twickenham on Saturday, May 19.
Humphreys commented: "Playing for my home province has been the pinnacle of my career and I have savoured every moment.
"However, after discussions with Brian Smith, I have decided to join London Irish on a long-term deal, and be part of a group that aims to re-establish London Irish as a force in the Premiership, with a strong Irish identity.
"With my family's future now secure, the next three weeks will be concentrated fully on the Ulster team where we will be doing everything possible to achieve our ambition of winning the Heineken Cup.
"I would like to thank everyone linked to Ulster Rugby for all the support they have given me over the last four years."
Ulster head coach Brian McLaughlin thanked Humphreys for his involvement over the past four years:
"Everyone at Ulster would like to that Ian for the role he has played in helping to turn the fortunes of the team around," he said.
"He has been an excellent servant since he returned to play in the province four years ago and his performances have contributed to Ulster enjoying one of the most successful periods in their recent history.
"The squad depth has improved considerably in the time that Ian has been with us and we are fortunate to have a number of contenders for the number 10 shirt.
"Paddy Jackson is a prodigious talent who has played very well this season, while Stuart Olding and Ruan Pienaar are also options for us.
"I am keen to stress that the job is not yet finished for Ian and he is still very much in contention to play in the Heineken Cup final in two weeks time.
"There would be no better way for Ian to finish his Ulster career than with a Heineken Cup winners' medal."
Ulster Rugby are hoping to finalise their squad for the 2012/13 season in the coming weeks.