"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 co-operate 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.
Al Jazeera's Yvonne Ndege, reporting from Accra, said that Obama is expected to deliver harsh criticism towards corruption in African countries.
"He is expected to criticise African leaders who have been corrupt, or are involved in corrupt practices," she said.
"Obama will also discuss links between aid to the continent, good governance and political stability."
The US president is also due to meet John Atta Mills, the president of Ghana, who was elected in a peaceful, transparent vote last December.
Ghana has in recent years been cast as an African success story, having a stable democracy where the level of poverty has halved over the last 15 years.
John Kufuor, a former Ghanaian president, told Al Jazeera that Obama was "coming to Ghana as a beacon of good governance [and] democratic practice".
"He wants to come here so as to encourage other countries in Africa to go in the direction of Ghana,” he said.
West Africa's abundance of natural resources and the recent discovery of oil in Ghana is also believed to be a factor behind Obama's trip.
"Part of the reason that we're travelling to Ghana is because you've got there a functioning democracy, a president who's serious about reducing corruption, and you've seen significant economic growth," Obama said before leaving Italy for Ghana.
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.
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."
The authorities in Cape Coast, which lies about 160km west of the capital, have suspended funerals in the run-up to Obama's visit to a castle in the town that was once used as a slave trading post.
"The dead can be buried later," said Ama Benyiwaa Doe, Ghana's central regional minister.
"We banned all funeral activities in Cape Coast because we want to give a befitting welcome to the US president.
"Obama is here for once and we must pay all attention to him."