Marchers arrived at Goodman Gallery in Johannesburg at about noon on Tuesday to protest against The Spear painting, which depicts President Jacob Zuma with his genitals exposed.
ANC representatives were preparing to hand over a memorandum demanding that the artwork no longer be included in an exhibition.
Riot police with shields and Johannesburg metro police on horseback kept protesters several metres away from the building.
ANC national spokesman Jackson Mthembu said the protesters were there to defend the dignity of the ANC.
“Even workers demand the right of human dignity for Jacob Zuma,” he said.
The crowd, which stretched over three blocks, was slow to move as busloads of protesters continued to arrive at Zoo Lake well after 10am, its planned start time.
A heavy police contingent kept close watch, with helicopters hovering over marchers and policemen blocking off side streets into the plush northern suburbs.
Municipal workers dressed in orange overalls joined the mass protest which started to move at about 11.45am, nearly two hours later than its scheduled start time.
Jan Smuts Avenue, one of Johannesburg's busiest routes linking the Johannesburg city centre with the northern suburbs, was closed between Zoo Lake and Bolton Road in Rosebank.
Buses, including some with registrations from Limpopo and Mpumalanga, lined the route.
The march was to protest the exhibition of the painting by artist Brett Murray showing Zuma's genitals.
A member of the public, Sipho Mweli, said he came from Mpumalanga to join the protest and to support Zuma.
Around his neck he had hung a cardboard placard on which he had written, “Draw your white father naked not our president.”
He said the statement was aimed at artist Brett Murray and he challenged him to draw a white man in the manner he had drawn Zuma.
Elijah Tauraza, also from Mpumalanga, said the painting was intended to belittle Zuma.
“How do you portray the president exposed when you have not seen him that way, even when he grew up?” he said.
The painting by Murray needed to be destroyed, he said.
“Keeping it in any form was an insult to Zuma and South Africans,” he said.
Gwede Mantashe, ANC secretary-general, was also part of the protest. - Sapa