Once credited with saving the country from apartheid, the ANC is increasingly under fire for corruption, mismanagement and failing to uplift its poorest people fast enough.
Today, one third of its local councils are rated as “dysfunctional” and often violent protests over a lack of water, electricity, rubbish and sewage clearance have doubled in recent years.
President Jacob Zuma has been mired in a series of scandals which are thought to have damaged the party’s standing as a whole. In December, he swapped finance ministers three times in five days in a bid to parachute a crony into the top job, wiping billons of rand from South Africans' pensions and savings.
This year, South Africa’s Constitutional Court ordered him to pay back public money spent on his private country estate and another suggested he should be prosecuted over alleged corruption relating to an historic arms deal.
Polls predict that the ANC could now lose majority control over its two most important cities, the capital Pretoria and the business capital Johannesburg, along with the seaside industrial hub of Port Elizabeth.
Instead, the lead opposition party the Democratic Alliance, which already runs the city of Cape Town and its surrounding province, could win majority control or form coalitions with other opposition groups to oust the ANC.
Ranjeni Munusamy, associate editor of the Daily Maverick news analysis website, said that while the ANC always experiences a last-minute electoral bounce because of residual loyalty to it as the party of liberation, the levels of undecided voters indicated by the polls suggested it could be in for a bruising time.
“I think we have now reached an unprecedented level of disenchantment and that’s evident from the amount of protest action and also because of the time elapsed since apartheid,” she said.
“Every year the situation has got worse, more people are unemployed. The economic crisis the president plunged the country into in December is still fresh in people’s minds and they may punish the ANC for that.”
Another unknown factor this year is the Economic Freedom Fighters party set up three years ago by socialist firebrand Julius Malema after he was ousted as ANC youth leader for indiscipline.
The EFF’s pledge to nationalise mines and banks and reclaim black land from whites struck a chord with impoverished, desperate and jobless South Africans, seeing it win 25 of the 400 parliamentary seats in the 2014 national elections.
Its MPs’ spirited protests against Mr Zuma in parliament, the broadening of its leftist policy agenda and the perception in some quarters that the Democratic Alliance is a party for whites has seen it attract a growing number of middle-class black South Africans.
Patric Mtshaulana, a barrister who trained ANC members in exile during apartheid who represented Mr Malema in his disciplinary hearing, suggested the EFF could overtake the DA as the official opposition.
“The DA is reaching its ceiling and young intellectuals are defecting towards the EFF, that’s the real threat to the ANC now,” he said.
In a blow to the ANC, its former president Thabo Mbeki, who was ousted by Mr Zuma and makes no secret of his dismay at the direction he has taken the party, met the EFF’s leadership at his Johannesburg home on Monday and posed for pictures afterwards.
All the parties have sought to evoke the memory of Nelson Mandela to their cause. Mmusi Maimane, a former preacher from Soweto who leaders the DA, said the ANC had abandoned his values, which only he could now be trusted to take forward.
It prompted Winnie Madikizela-Mandela, the former president’s wife, to accuse the DA of being “morally, ethically and intellectually bankrupt”.
Meanwhile President Jacob Zuma has told voters that “God and Jesus” would vote ANC and that if they did not want a return to apartheid, they should follow suit.
“The ancestors are turning their backs against you if you leave the ANC and you will have bad luck,” he told Soweto residents. “It's not nice outside the ANC.”
Polls open at 7am South African time until 7pm and the first results are expected early on Thursday morning.