The 46-year-old has taken charge of a record 68 internationals, and has been on the South Africa Rugby Union's elite panel for 21 years.
Kaplan has also refereed more Super Rugby and Currie Cup matches than any other official, and will reach a century of Super Rugby fixtures when he takes charge of the game between the Cheetahs and the Sharks later this month.
"Rugby has been my life for the past few decades and I've made the decision with a tinge of sadness," said Kaplan in a SARU statement.
"But the time has come to move on and make way for the young referees we have coming through in South Africa.
"I've had an incredible career, and I'd like to thank both SARU and the IRB for the opportunities they have given me.
"I've always prided myself on having the best interests of the game at heart and being brave enough to try and get the best out of every game in which I have been involved. I'll miss my front-row seats on the big stage."
Kaplan is best known in the northern hemisphere for being involved in the controversial 'Ballgate' incident at the 2011 Six Nations meeting between Wales and Ireland.
Wales won 19-13 after scrum-half Mike Phillips' crucial try was wrongly allowed to stand, despite the home side taking a quick throw-in with a different ball to the one kicked off the field.