Obama, who will address the service, and First Lady Michelle Obama were accompanied by former President George W Bush and his wife Laura aboard Air Force One.
Former Secretary of State Hillary Clinton also joined them abroad the special aircraft to attend the memorial service at the FNB soccer stadium in Johannesburg.
Former US President Bill Clinton and his daughter Chelsea Clinton, who are attending an event in Rio de Janeiro, will travel to Johannesburg.
It is very rare for an event to be attended by four American Presidents.
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Deputy National Security Adviser Ben Rhodes said Obama will speak during the memorial service. He said the US has full confidence in South Africa's security measures.
"South Africa's hosted the World Cup so they have experience hosting significant crowds and hosting events like this," he said.
US Vice President Joe Biden has signed a condolence book at the South African embassy here. He will honour Mandela by speaking on Wednesday at a memorial service for the statesman at the National Cathedral.