With results in from 8.5% of polling stations, the pro-business Democratic Alliance (DA) was on 27.52% while the Marxist Economic Freedom Fighters party (EFF) was on 7.72%, according to data from the Independent Electoral Commission, Reuters reported.
If the final results were to resemble the early picture, that would represent a seismic shift in South African politics after 30 years of ANC government, forcing the ruling party to make a deal with one or more other parties to govern.
The ANC has won national elections held every five years since the landmark 1994 election, which marked the end of apartheid and the ascent of Nelson Mandela as president.
But since those heady days the ANC's support has declined because of disillusionment over issues like high unemployment and crime, frequent power blackouts and corruption.
Voters are electing provincial assemblies in each of the country's nine provinces, and a new national parliament which will then choose the next president.
With the ANC still on course to get the largest share of the vote, its leader President Cyril Ramaphosa is likely to remain in office - unless he faces a leadership challenge from within party ranks.