"It is with mixed feelings that I announce my retirement from Ulster Rugby as of the end of this season," the 36-year-old hooker, who had previously flagged up his likely international retirement, said in a statement.
"This feels like the right time for me to go out on my terms, a luxury for which I feel very privileged."
Best, whose contract expires after the September-November World Cup, has spent 15 seasons at the top level and helped Ireland win the Six Nations four times including two Grand Slam triumphs.
He has also toured Australia and New Zealand with the British and Irish Lions in 2013 and 2017 respectively and has 116 international caps.
Best also captained Ireland to their first win over New Zealand in 2016.
(Reporting by Alan Baldwin in London, editing by Toby Davis)
