South Africa's President Jacob Zuma will face a challenge for the leadership of the ANC next week from his deputy, Kgalema Motlanthe.
Mr Motlanthe's spokesman Thabo Masebe said that Mr Motlanthe had accepted his nomination to stand as ANC leader.
Mr Zuma has received most nominations, but his critics say he has failed to tackle South Africa's problems.
The African National Congress leader will be overwhelming favourite to win elections due in 2014.
The ANC has gained more than 60% of the vote in each of the national elections held since the end of white minority rule in 1994.
But it is facing increasing accusations that it is not doing enough to boost economic growth, or to combat corruption.
Mr Masebe said Mr Motlanthe had agreed to run for the ANC leadership after being nominated by the most branches in three of South Africa's nine provinces.
"He's always said branches must be given a chance to express their free will," Mr Masebe said.
Mr Motlanthe was also available to continue serving as deputy president, or as a member of the party's national executive committee, he said.
Although there has been months of speculation that Mr Motlanthe would run against Mr Zuma, this is the first confirmation that he would accept his nomination.
He previously said he was "agonizing" over the decision.
The ANC, which is marking its centenary, will hold leadership elections at its conference in Mangaung which starts on Sunday.
Analysts say Mr Zuma is likely to be re-elected, having majority support in the remaining six provinces.
Mr Zuma was elected ANC leader at its last conference in 2007 following a bruising battle with then-President Thabo Mbeki.
Mr Motlanthe backed Mr Zuma, and became his deputy in the ANC and the government.
Mr Zuma's allies were hoping that Mr Motlanthe would step back from challenging him at the last minute in order to avoid worsening divisions in the party, analysts say.
Mr Masebe said Mr Motlanthe did not believe his candidature was divisive.
"The ANC is a democratic organisation... He [Mr Motlanthe] wants to avail himself to serve the organisation in any capacity the conference decides," Mr Masebe added.
Powerful Congress of South African Trade Unions (Cosatu) General-Secretary Zwelinzima Vavi said the ANC needed to move away from "a politics based on narrow ambition and accumulation" of wealth.
"There is a poisoned atmosphere of divisions, and fast-moving cliques and cabals," he said.
Cosatu, which is allied to the ANC, has called on the party to retain Mr Zuma and Mr Motlanthe in their current posts.
But Mr Motlanthe risks losing his job as deputy president if business tycoon Cyril Ramaphosa, who played a key role in the fight against apartheid, decides to run for the post, analysts say.
Most pro-Zuma ANC branches have nominated Mr Ramaphosa for the post of deputy leader.
The ANC Youth League said it welcomed Mr Motlanthe's candidature with great excitement and jubilation.
"Comrade Kgalema Motlanthe, a fearless leader who refused to be intimidated and stood by ANC principle, is indeed the future of the ANC and the future of South Africa," it said.
Mr Motlanthe served for six months as South Africa's caretaker president after Mr Mbeki was forced to resign in 2008.
The ANC Youth League has been at the forefront of the campaign to oust Mr Zuma, arguing that he has failed to tackle poverty and unemployment.
Its leader Julius Malema was expelled from the ANC last year for indiscipline after he attacked Mr Zuma's leadership.
South Africa has been hit by a series of wildcat strikes this year.
In August, police shot dead 34 striking workers at the Marikana mine in South Africa's North West province.
It was the most deadly police action since the ANC took power in South Africa's first democratic elections.