Mrs Clinton is on the second leg of an 11-day African tour
US Secretary of State Hillary Clinton has held talks with South African President Jacob Zuma in Durban.
After the meeting, both talked of strengthening ties between the US and Africa's largest economy.
Mr Zuma, who took office in May, said the new administrations were taking their relationship to "a higher level".
They also discussed HIV/Aids, the cause and treatment of which has, in the past, been a source of friction between the two countries.
"In both countries there are new administrations which are taking that relationship to a level higher. That is what we are trying to do," Mr Zuma said following the 45-minute discussions.
Mrs Clinton is on the second leg of an African tour which will take her to Angola on Sunday before she heads to Nigeria, Liberia, the Democratic Republic of Congo and Cape Verde.
The situation in neighbouring Zimbabwe, as well as in Sudan and Somalia, was also discussed.
Later on Saturday, Mrs Clinton visited a housing project in Cape Town and met South Africa's last white leader, FW de Klerk, who shares a Nobel Peace Prize with anti-apartheid leader Nelson Mandela for their role in ending apartheid.
On Friday, Mrs Clinton described her meeting with Mr Mandela as inspirational.
South African officials hope that the visit by Mrs Clinton will signal a new period of cooperation to support the already strong business links between the two countries.
The two countries previously had uneasy relations when governed by South Africa's President Thabo Mbeki and his American counterpart George W Bush, with disagreements over Zimbabwe, the fight against AIDS, and the US-led invasion of Iraq.