The president will make two stops at sights that highlight the continent's harsh racial history: Senegal's Goree Island, which was the center of Atlantic slave trade and Robben Island, the apartheid-era prison in South Africa where Mandela spent 18 years of his 27 years in prison.
The White House is closely monitoring Mandela's health, which has added a degree of uncertainty to Obama's travel itinerary. The 94-year-old anti-apartheid leader has been hospitalized for about three weeks with a reoccurring lung infection and South African officials have now deemed his condition critical.
Obama advisers have been reluctant to publicly discuss what impact his condition might have on Obama's trip. There had been no formal plans for the two men to meet, though Obama aides did leave open the possibility of the U.S. president meeting with Mandela's family.
"Ultimately, we want whatever is in the best interest of his health and the peace of mind of the Mandela family," said Ben Rhodes, Obama's deputy national security adviser.
The president had no public events planned Wednesday after his arrival. He was scheduled to spend Thursday meeting with Senagalese President Macky Sall, then meet with civil society leaders at Goree Island.
Top White House economic advisers and U.S. business leaders were traveling with Obama, underscoring the trip's focus on boosting American economic ties with Africa. Six of the world's 10 fastest-growing economies last year were in Africa, according to the World Bank.
While the U.S. has been slow to ramp up its trade with Africa, China, along with India, Malaysia and Brazil, have been building robust economic relationships on the continent. Chinese officials say Beijing's trade with China totaled $200 billion last year. The U.S. Trade Representative said American trade with Africa reached $95 billion in 2011.