The ANC held an unbeatable lead with 57.73 percent of the votes after 95 percent of voting districts were officially tallied following Wednesday's vote.
That means they will be mathematically assured more than 50 percent of votes cast in the final official tally, which due to be announced Saturday, and a similar proportion of parliamentary seats.
The ANC has been in power since 1994 but the result would be the party's worst national showing since Nelson Mandela led the party to victory in the first multi-racial polls after apartheid ended in 1994.
President Cyril Ramaphosa took over last year when the party forced the then-president Jacob Zuma to resign after nine years dominated by corruption allegations and economic problems.
Results released by the Independent Election Commission showed the ANC's closest rival, the Democratic Alliance, trailing with 22 percent of the vote.
The Economic Freedom Fighters, founded six years ago by the former ANC youth leader Julius Malema, was in third place with almost 10 percent.
The party that wins the most seats in parliament selects the president, who will be sworn in on 25 May.