Irish, who will join the English Premiership next season after winning promotion, announced the signing of the Test centurion on social media on Monday night.
Kepu has been a mainstay of Australian Test rugby and the Waratahs for more than a decade, playing 135 Super Rugby matches and 103 Test matches.
Waratahs coach Daryl Gibson said Kepu would leave a hole at the Waratahs, but also had provided a strong foundation for the next generation to develop.
"Sekope has become a real leader for the team and will leave with a reputation of strong scrummaging and a running and passing skill-set that rivals a centre. He is an absolute gentlemen of the game and will be missed," he said.
“He will also leave a legacy for young aspiring props who have benefitted from his knowledge and willingness to nurture the next generation. I hope to see him back one day and serve the sport as a coach.
"Being a longstanding member of the Waratahs, his influence I'm sure will be felt for many years yet.
“There are many of our younger blokes who have benefited from training and playing alongside Sekope and while we will be sad to lose him, it will make way for the next generation to step up," said Gibson.
Father-of-four Kepu said his move came at a good time for himself and his young family.
“It’s great opportunity for my family to try something new and I think it’s the right time for us to move. My family is very important for me," he said.
“I’m excited to be able to go to a club with a lot of history and play in a different competition.
“But right now I’m in the middle of the Super Rugby season and I very much want to give everything I have to the Tahs.
“I’ll be doing my best over the next few months, whatever I can do to contribute to the team on and off the field.
“I’ve only ever played for one Club in Super Rugby and I’ve had the most enjoyable time with the Waratahs."
This is not the first time Kepu has dipped his toes overseas - the 33-year-old joined French club Bordeaux briefly after the 2015 Rugby World Cup but returned to Australia for family reasons.
Kepu joins teammates Nick Phipps and Curtis Rona in signing on with London Irish for the 2019-20 season and beyond.