Chris Morris has been called up as his replacement for the mega-event, commencing on May 30 in the UK.
Nortje overcame ankle and shoulder injuries over the course of the summer before he could make his international debut in March this year. On the basis of his performances, the 25-year-old was selected in South Africa's World Cup squad.
Unfortunately, Nortje fractured his right thumb while practising in the nets, and it has now been confirmed that he would need six to eight weeks rest to recover fully.
The 32-year-old all-rounder Morris, who has not played an ODI in more than a year, has replaced Nortje in the 15-member squad.
Morris is currently playing at the IPL with Delhi Capitals, for whom he has taken 13 wickets in nine games this season.
South Africa Squad: Faf du Plessis (c), JP Duminy, David Miller, Dale Steyn, Andile Phehlukwayo, Imran Tahir, Kagiso Rabada, Dwaine Pretorius, Quinton de Kock (wk), Chris Morris, Lungi Ngidi, Aiden Markram, Rassie van der Dussen, Hashim Amla, Tabraiz Shamsi.