An experienced diplomat, Dlamini-Zuma, 63, is known for her competent management and stern personality.
A doctor by training, she was health minister when Mandela became the country’s first black leader.
She went on to be foreign minister for a decade earning praise for her shuttle diplomacy to end the war in the Democratic Republic of Congo.
But critics picked faults with her “quiet diplomacy” towards neighbour Zimbabwe, during a crisis that saw President Robert Mugabe evict thousands of white farmers from their land in 2000.
Her ex-husband President Jacob Zuma named her interior minister, a job that was seen as a demotion, but won her plaudits for turning around a ministry mired in gross mismanagement to achieve the first clean audit in 16 years.
If elected to the pan-African bloc’s top job, she has vowed to work at making “it a more efficient and effective organisation”.
Squaring off against French-speaker Ping of Gabon, she has refused to be labelled an English-speaking candidate.
“I am not Anglophone, I’m Zulu,” she said, adding that when she gets to work she will be “implementing programmes… agreed upon by everybody” rather than “consulting the anglophone and the francophone.”
Dlamini-Zuma however enjoys the backing of the predominantly English-speaking southern African region, which has never held the top Commission job since the AU was created a decade ago.
“She takes her work very seriously,” said Prince Mashele, an analyst at the Centre for Politics and Research, who worked with Dlamini-Zuma’s ministry when she was foreign minister.
“She has the rare quality of putting up very good administrators,” Mashele added.
But she has raised eyebrows with her unsmiling demeanour.
“I thought she could do better if she was a little more affable,” said Mashele.
If elected by the AU’s 54 leaders at a summit opening on Sunday, she would become the first woman to head the AU Commission.
Born January 27, 1949, in the eastern province of KwaZulu-Natal, Dlamini-Zuma took up politics in high school.
In the 1970s she went into exile, and studied at Britain’s universities of Bristol and Liverpool, while helping organise the anti-apartheid movement overseas.
She met Zuma while working as a paediatrician at a Swaziland hospital and became the polygamist president’s third wife in 1982. They divorced in 1998.
When the ban was lifted on the African National Congress in 1990, she returned home.
After the first democratic elections she was tapped by Mandela to transform the country’s segregated health system.
She is remembered for introducing legislation that overhauled the highly unequal system and gave the poor access to free basic care, but has also been criticised for championing a controversial HIV drug that was later proved ineffective.
When Zuma fell out with ex-president Thabo Mbeki and moved to oust him as ANC leader in 2007, she stood as Mbeki’s running mate for the ANC presidency.
But when Zuma won party polls and later become president, kept his ex-wife in his cabinet — a rare Mbeki ally to avoid the boot.
“She is an astute politician, a veteran, the experience she acquired as foreign minister puts her in good stead to take over this role” at the AU, said Keith Gottschalk from the University of the Western Cape.