An air force plane carrying Mandela's casket took off from here after up to 100,000 people filed past his body during the three days it lay in state at the Union Buildings in Pretoria.
The same venue had witnessed his inauguration as South Africa's first black President in 1994.
Thousands had packed a stadium in Soweto for a memorial service for Mandela on Tuesday, an event which saw many world leaders, including President Pranab Mukherjee and US President Barack Obama, coming together to pay homage to the elder statesman.
Members of Mandela's family accompanied his remains to Qunu, the village where he had wanted to spend his final days. He will be buried tomorrow in a state funeral incorporating burial rites of his Xhosa tribe.
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The Hercules C-130 transport aircraft, escorted by two Gripen fighter jets, took off from Waterkloof airbase after a farewell ceremony organised by the African National Congress. The occasion was the party's final tribute to the man who demolished apartheid and brought it to power.
President Jacob Zuma and other ANC leaders attended the event, which included a multi-faith service and a musical tribute. More than 1,000 members of the ANC attended the ceremony that was broadcast live on television.
Mourners heard Zuma pay his own tribute to Mandela, calling him a "towering figure" and "a man of action".
"Yes, we will miss him... He was our father, he was our guardian. He was something special. We'll always keep you in our hearts," Zuma said during the ceremony.
After the ceremony, two of Mandela's closest friends and fellow Robben Island prisoners, veteran Indian-origin anti-apartheid activist Ahmed Kathrada and Andrew Mlangeni, helped wheel his coffin onto the runway. It was loaded into a hearse and driven to the waiting Hercules plane.