His roots in Africa, through his Kenyan father, assure him a hero's welcome and he will deliver a message on the importance of good governance in a country that defies stereotypes of a continent blighted by conflict, coups and crisis.
Ghana's President John Atta Mills, due to meet Obama on Saturday, was elected in a peaceful, transparent vote last December.
Economic reforms in the cocoa and gold producing country, set to begin pumping oil next year, also helped bring unprecedented investment and growth before the impact of the global financial crisis.
Thousands of Ghanaians packed the dark streets around the airport, hoping for a glimpse of Obama.
"It's a great moment for Ghana and Africa. We have to celebrate our own," said driver Emmanuel Tsawe, who covered his 43-seater bus with Obama posters.
"I believe he has good intentions for the continent and we must cooperate with him," he said.
Obama will be welcomed by crowds that some estimate could be as large as 1.5 million in the capital, Accra.
But Africa has not been a top priority for an administration grappling with the global financial crisis.
Few expect a shift in policy and the main message will be on the importance of good governance and the wise use of aid, such as the G8 commitment made in Italy to spend $20 billion on improving food security in poor countries.
Obama drew on his own background to stress the importance of transparency and strong institutions in bringing change.
"My father travelled to the United States a mere 50 years ago and yet now I have family members who live in villages -- they themselves are not going hungry, but live in villages where hunger is real," he said.
"If you talk to people on the ground in Africa, certainly in Kenya, they will say that part of the issue here is the institutions aren't working for ordinary people. And so governance is a vital concern that has to be addressed."
Obama was due to address parliament on Saturday before visiting Cape Coast Castle, a fort used in the transatlantic slave trade. He and his wife Michelle will spend less than 24 hours in Ghana before returning to the United States.