Du Plessis left the field during the first one-day international in Durban on Thursday with what he thought was a minor injury to his right index finger.
But Cricket South Africa announced ahead of Sunday’s second match in the six-match series that the finger was broken.
He will be out of action for between three and six weeks and will aim to be fit in time for the first of four Tests against Australia, starting in Durban on March 1.
It had previously been announced that former captain AB de Villiers would miss the first three one-day matches, also with a finger injury. A captain for the rest of the series will be announced on Saturday.
Batsman Farhaan Behardien and wicketkeeper-batsman Heinrich Klaasen have been added to the squad.