The pacer, who played the last of his 101 Tests in December 2009 but has been out of favour with the national selectors ever since, will make one final appearance in a Twenty20 [ Images ] international against India [ Images ] in Durban on January 9.
"It has been a wonderful journey for me to represent my country," Ntini said in a statement. "I have so many great memories, which I will carry with me for the rest of my life," the 33-year-old said in a statement on Tuesday.
Ntini made his South Africa debut in a one-day international in 1998. He claimed 390 Test wickets, with best figures of 7-37, and 266 wickets in 173 ODIs.
Nicknamed the 'Mdingi Express" after the village of his birth in the Eastern Cape, Ntini will continue to play domestic cricket.
"My career is by no means over; it just means that internationally my time has come to hang up my boots. Domestic cricket is thriving at the moment, and I want to be a part of the set up, as a player, for as long as possible," he said.