South African President Jacob Zuma has said military intervention is not the right approach to the crisis in Libya.
Speaking at a news conference in Pretoria alongside David Cameron, Mr Zuma said the fate of Col Gaddafi should only be decided by negotiation.
The UK prime minister said there were differences between African leaders and Nato over the military operation.
He is in Johannesburg for the start of a trip to bolster Britain's business links with Africa.
Mr Cameron said Nato and African leaders all shared the goal of seeing Col Gaddafi step aside as Libyan leader.
But Mr Zuma said Nato bombing raids did not help the political situation in Libya, and repeated the African Union's (AU) call for a negotiated departure for Col Gaddafi.
He said: "Once there was a fight the AU took a very clear position, that the military intervention would not solve the problem. You needed political intervention. And the AU has worked out a clear roadmap, what needs to be done.
"We feel, as the African countries, the Libyan people must decide their destiny, they must negotiate, they must discuss any demand, any condition that is put forward. Gaddafi, on his side, has said he's not going to be part of the processes that discusses the change in Libya [but] he will give it a chance.
"So our view, from the AU point of view, is that what happens finally to Gaddafi must be as a result and an outcome of the Libyan people."
Meanwhile, it is understood that Mr Cameron's trip has been cut back so he could return to the UK to deal with the ongoing row over phone-hacking by journalists.
The BBC's deputy political editor James Landale said initially the trip had been pencilled in for five days, rather than the two limiting it to South Africa and Nigeria.
He said another overseas visit may have been seen as risky for a prime minister who only 12 days ago was in Afghanistan when the phone-hacking row broke.
Mr Cameron is under pressure over his decision to employ former News of the World editor Andy Coulson as his press spokesman.
Mr Coulson, who has since left No 10, has been arrested and bailed as part of an inquiry into allegations journalists at the newspaper illegally hacked into mobile phone messages.
Some MPs believe Mr Cameron's trip to Africa - as the phone-hacking scandal continues to unfold in the UK - could leave him vulnerable.
But Downing Street said the trip had been shortened "simply because the prime minister has other things he wants to be focused on".
During the trip, Mr Cameron will give strong backing to plans for a 26-nation African free trade area intended to cover 600 million people and more than half the area of the continent within three years.
He will say the concept could increase the continent's GDP by £38bn ($62bn) - £12bn ($20bn) more than the world's entire annual aid budget for sub-Saharan Africa.
Writing in South Africa's Business Day, Mr Cameron said: "In the past, there were marches in the West to drop the debt. There were concerts to increase aid.
"And it was right that the world responded.
"But they have never once had a march or a concert to call for what will in the long term save far more lives and do far more good - an African free trade area. The key to Africa's progress is not just aid. It is time for some fresh thinking."
This week's trip is the latest in a series of trade missions which have seen Mr Cameron visit China and India, and Deputy Prime Minister Nick Clegg travel to Mexico and Brazil, in a government push to deepen UK links with the emerging economies expected to act as the drivers of global growth in coming years.
Development Secretary Andrew Mitchell, trade and investment minister Lord Green and a business delegation comprising 25 representatives from a range of blue chip companies, private equity firms and small businesses are accompanying the prime minister.
Barclays chief executive Bob Diamond, Premier League communications director Bill Bush and senior executives from Waitrose and Vodafone are also on the trip.