He has maintained his spiritual leadership in India after fleeing China and has been outspoken on Chinese abuses in Tibet. Although China and South Africa have a growing trade relationship, the government has not commented on the reason for the denial of entry.
It is the third time the Dalai Lama, a winner of the Nobel Prize, has been refused a visa by South Africa. A 2009 peace conference in Johannesburg was cancelled after it was learned he could not attend.
In 2011, he was unable to speak at a conference in celebration of fellow Nobelist Archbishop Emeritus Desmond Tutu's 80th birthday, after Tutu personally invited him. South Africa's immigration office said at the time the Dalai Lama himself withdrew his application for a visa.
The Dalai Lama, 79, was to attend a World Summit of Nobel Prize Laureates in Cape Town in October, and the refusal of the visa could provoke a boycott of the event.
"I have heard that if the Dalai Lama is not allowed into the country, other invited guests have said they will not come," Tutu's spokesman Roger Friedman said.
Host of the event, Cape Town Mayor Patricia de Lille, said she would ascertain why the visa was denied.
"We have not heard from them yet, but I will not give up hope that our government will not humiliate the Dalai Lama again," she said.