In dramatic scenes, Ramaphosa and top ANC officials left an all-night party executive meeting outside Pretoria in a heavily-guarded police convoy to drive to Zuma's residence to again demand he resign - which Zuma flatly refused.
This raises the possibility that Mr Ramaphosa, who is deputy president, could replace Mr Zuma by the weekend or even earlier. He is fighting the reinstatement of corruption charges that were dismissed before he became president over a 30 billion-rand (now £1.8 billion) government arms deal arranged in the late 1990s.
The Guptas and Zuma have denied all allegations of wrongdoing.
ANC members are intensifying pressure on Zuma to resign, telling the media he will do so on Wednesday. Spokesmen for both the presidency and the ANC remained unavailable for comment.
Jackson Mthembu, the ANC chief whip, said parliament would now vote on a no-confidence motion on Thursday.
The ANC can "recall" the head of state, essentially forcing him to resign, but the process is a party-level instruction and he is under no constitutional obligation to obey. Neither of these appeared to yet be in play for the ANC, although the opposition Economic Freedom Fighters party has already submitted a motion for a parliamentary vote of no confidence.
The party of embattled South African president Jacob Zuma has finally told him to go after weeks of uncertainty.
Earlier, the spokesperson of the Hawks, Hangwani Mulaudzi, had confirmed the raid to journalists waiting outside the Gupta home.
"The investigations and action simply can not end [with the Guptas] and must continue to all those implicated, including key ministers", Zakhele Mbehle from the Democratic Alliance said in a statement.
Its motion will be amended by the ruling African National Congress (ANC) to retain the "no confidence" elements but with a different preamble and reasoning. "We're not playing around in terms of making sure that those who are responsible in the so-called state capture, they take responsibility for it", Mulaudzi said.
Mr Zuma broke his silence on Wednesday in a live interview with state broadcaster SABC as the nation awaited word on whether he would obey a ruling party order to leave office.
The ANC's former head of intelligence, Zuma, 75, took office in May 2009, just weeks after prosecutors dropped graft charges against him.