Dwindling popular support, corruption scandals and rampant in-fighting mean that the contest looks set to be a bitter battle exposing divisions at the heart of the party.
The contenders will face each other at the African National Congress' (ANC) 54th national elective conference in December when Zuma is expected to stand down as party chief.
The likely frontrunners are outgoing African Union chairwoman Nkosazana Dlamini-Zuma, who is Zuma's former wife, and Deputy President Cyril Ramaphosa.
The ANC's powerful women's league opened the campaign for the party's top job when earlier this month it called for a female leader -- a clear endorsement of Dlamini-Zuma.
Dlamini-Zuma, who has four children with President Zuma, is the head of the African Union Commission.
She is not seeking a second mandate for the role, fuelling speculation that she hopes to succeed her ex-husband at the ANC's helm -- though she has yet to declare her candidacy.
The succession battle is seen as crucial for Zuma's future because if a political adversary is chosen it could mean that he is forced to step aside before the end of his term, according to political analyst Ralph Mathekga.
"He is trying to have his wife run for ANC president, first of all as she is highly unlikely to go after him on some of the corruption charges," said Mathekga.
Zuma appeared to throw his weight behind 67-year-old Dlamini-Zuma -- who has held a string of ministerial posts including the foreign and home affairs portfolios -- earlier this month when he told public radio that the ANC "is ready" to elect a woman as its leader.
"She remains a mystery candidate when it comes to her vision for a future South Africa," he added.
Cyril Ramaphosa, 64, is also expected to run for the party's top job.
A former trade unionist who helped negotiate the end of white-minority rule in 1994 and then became a wealthy businessman, Ramaphosa told Power FM radio last month that he is "available to stand", though he stopped short of a formal declaration.
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