Mbeki, who took over from Nelson Mandela as president in 1999, agreed on Saturday to accept the ruling ANC’s request that he resign before the end of his term next year.
"I would like to take this opportunity to inform the nation that today I have handed a letter to the speaker of the national assembly…to tender my resignation from the high position of president of the Republic of South Africa," said Mbeki in a live speech on national broadcaster SABC.
The resignation will be effective from a date to be decided by parliament, said Mbeki, looking subdued during his speech.
Militants in the ANC led the charge to oust Mbeki about a week after a judge who threw out corruption charges against Zuma suggested there was high-level political meddling in the case.
The fatal political blow came just after Mbeki scored his biggest foreign policy coup by mediating a power-sharing deal in Zimbabwe.
An acting president is expected to be announced on Monday, ANC treasurer-general Mathews Phosa said in a televised debate on SABC1. "And he or she will announce the next Cabinet."
Phosa said the ANC wants the cabinet to remain, underscoring concerns that the departure of experienced, pro-Mbeki ministers could hurt the country.
"We want the Cabinet to stay. We are very happy if they stay and we do these things together," he said.
Mbeki’s brother, Moeletsi Mbeki, a political analyst who has been critical of Mbeki’s policies, was quoted in a newspaper as saying the ANC’s ousting of Mbeki was a "recipe for civil war" that set a dangerous precedent.
South Africa’s leaders had since the country’s first multi-party election in 1994 embarked on policies "directed at pulling the people of South Africa out of the morass of poverty" and building a prosperous country, Thabo Mbeki said.
Mbeki has been credited with ensuring growth and attracting foreign investors to Africa’s biggest economy. He was also instrumental in building a black middle class.
But critics and Zuma’s allies in trade unions and the Communist Party say Mbeki was out of touch with millions of poor blacks.
South Africans, whose social and economic problems have been overshadowed by the fierce rivalry between Mbeki and Zuma, are bracing for a period of uncertainty and a deeply divided ANC is unlikely to ease their concerns over rampant crime, social ills and an AIDS epidemic ravaging millions, analysts say.
Supporters of Mbeki may split from the ANC and contest elections as a breakaway party in 2009, South Africa’s Sunday Times said.
The move threatens to shatter the foundations of the country’s post-apartheid political landscape, which has been dominated by the ANC since the end of apartheid.
Although Mbeki’s willingness to step down without a fight suggests a smooth transition of power, a number of ministers have threatened to resign rather than serve in a Zuma-controlled government.
The Sunday Times said Defence Minister Mosiuoa Lekota, Deputy Defence Minister Mluleki George and other Mbeki loyalists are planning to start a new party and organisers will meet this week to discuss the move.
Now that Mbeki is out of the picture, Zuma could come under pressure from his left-leaning allies in trade unions to ease poverty while he tries to win over the confidence of foreign investors who would not welcome more government spending.
"The main challenge is trying to end long-term uncertainty. If he can make progress in the fields of service delivery and unemployment and education it could go a long way," said Mike Davies, Middle East and Africa analyst at Eurasia Group.
Mbeki, who joined the ANC Youth League when he was 14, once said he was born into the struggle against apartheid and he struck that theme again when he made his last official speech.
"I have been a … member of the African National Congress for 52 years. I remain a member of the ANC and therefore respect its decisions," he said.