President Zuma is widely seen as favouring Dlamini-Zuma, with whom he has four children, ahead of Deputy President Cyril Ramaphosa.
Nkosazana Dlamini-Zuma, the former chief of the African Union, is a leading candidate to replace Zuma as head of the ruling ANC party in December and then as national president within two years.
President Zuma is widely seen as favouring Dlamini-Zuma, with whom he has four children, ahead of Deputy President Cyril Ramaphosa in the race that could split the African National Congress (ANC).
Dlamini-Zuma told AFP that she found it "offensive" to be seen as her ex-husband's chosen candidate to shield him from the courts when he leaves office.
"I will not be elected by President Jacob Zuma," she said after delivering a speech in Johannesburg.
"If I am elected, I will be elected by South Africans, and they will have reasons why they elect me -- and that is why I find it offensive."
Dlamini-Zuma, 68, a former health minister, has not publicly declared her candidacy in the ANC leadership battle.
But she has campaigned across the country in recent weeks, drumming up support ahead of the party conference in December where delegates will elect their new leader.
President Zuma, who completes his final term in power in 2019, faces multiple court cases including almost 800 corruption charges that may be reinstated over a multi-billion dollar arms deal in the 1990s.
Dlamini-Zuma was an anti-apartheid student activist who fled into exile in Britain to qualify as a doctor before meeting Jacob Zuma in Swaziland.
They married in 1982 and divorced in 1998.
"She is seen as one of the main contenders to take over from her ex-husband," the Institute of Security Studies think-tank said when she left the African Union position.
"It is alleged that she will protect Zuma and family members from prosecution for corruption if she becomes president."
Leading political commentator Ranjeni Munusamy wrote this week that Zuma backed Dlamini-Zuma "not because he is convinced she has marvellous leadership qualities, but for his own survival."
In her address to the Gordon Institute of Business Science, Dlamini-Zuma painted a stark picture of South Africa's challenges.
"The majority of our people remain landless, and the economy is stagnant, de-industrialising and dominated by monopolies which are predominantly both white and male," she said.
"A large number of people still live under conditions of squalor. And there are unacceptable levels of corruption both in public and private sector... the status quo is dangerous to all of us."
Dlamini-Zuma added that if she became president, she would hope to leave a legacy of boosting education and skills.
"If you have skilled work people, they figure out what to do with the minerals, where to get the finances, they figure out most things," she said.
A divisive succession battle between Dlamini-Zuma and wealthy former businessman Ramaphosa could lead to the ANC losing power in 2019 for the first time since it won the 1994 election under Nelson Mandela.