A court ruling, handed down on September 12, threw out charges of corruption against Zuma, saying the prosecuting team violated some of his procedural rights.
Mbeki's government has denied interfering in the case.
Gwede Mantashe, the ANC's secretary-general, insisted the decision to ask Mbeki to stand down had been taken in the interests of party unity.
"This is not a punishment," he said. "We decided to take this decision in an effort to heal and reunite the ANC."
Mbeki's term had been due to expire in mid-2009.
Under the South African constitution, the president is appointed by parliament, which has been dominated by the ANC since the end of apartheid and the start of majority rule in May 1994.
Al Jazeera's Bernard Smith, reporting from Johannesburg, said: "It seems like Mbeki is not going to fight this.
"It looks like he is going to end up resigning and then parliament will appoint a new president who will be in place until scheduled elections are called as early as April - between April and June - next year."
Analysts have predicted Baleka Mbete, the speaker of parliament, will be named the interim head of state until elections are held.