"Under your leadership, Ghana has been a beacon of democracy and a contributor to global peace and security," she said to the Ghanaian President after their meeting.
Akufo-Addo called for solidarity from the US for countries like Ghana to bring their economies "back on track."
He also voiced his concern that private American investors neglect the country and that he wants "to be able to change that dynamic."
However, the release of some of the aid money vowed by Harris might prove difficult due to partisan differences over the federal budget.
Harris was welcomed at Accra's Kotoka International airport by schoolchildren who cheered and waved Ghanaian and American flags.
Harris, who is being accompanied by her husband Douglas Emhoff on the trip, placed her hand on her heart and smiled broadly as she stepped off the plane after an overnight trip.
"We are looking forward to this trip as a further statement of the long and enduring and very important relationship and friendship between the people of the United States and those who live on the continent of Africa," Harris said.
She said she was "very excited about the future of Africa," adding that she would be discussing issues like increasing food security, climate change, and growing investment on the continent.
What's on the agenda?
Harris will spend three nights in Ghana, two nights in Tanzania, and one in Zambia. She is the highest-ranking member of the Biden administration to visit Africa this year.
She is due to deliver a speech in Accra and visit Cape Coast Castle, where enslaved Africans were once loaded onto ships bound for America.
She will meet with leaders of each country and lay a wreath to commemorate the 1998 bombing of the US embassy in Dar es Salaam, in Tanzania.
Her agenda also includes several less traditional stops to highlight the future of the continent where the median age is just 19.
Though White House officials have stressed Harris's trip concerns the US relationship with Africa only, the continent remains of great strategic importance as the US recalibrates its foreign policy with a focus on China.
China has established an enormous presence on the continent, whether by expanding telecommunication networks or building infrastructure.
Ghana reached a $2 billion (€1.8 billion) deal with a Chinese company to develop roads and other projects in return for access to a key mineral for producing aluminum.
While Ghana is one of the continent's most stable democracies, its economy faces a debt crisis and soaring inflation.