President Akufo-Addo greeted VP Harris outside the Jubilee House presidential palace in the capital Accra before their bilateral meeting.
"We're looking forward to using this visit of yours as a springboard to renew these relationships and expand them," the Ghanaian leader said.
Harris' office said the US would provide Ghana with $139 million in bilateral assistance next year, including for economic, business and culture initiatives, and for the health sector such as an anti-malaria program.
Washington will send a special advisor to Ghana to help Akufo-Addo's government with its debt profile this year.
"The US Department of the Treasury's Office of Technical Assistance will deploy a full-time resident advisor in 2023, to Accra to assist the Ministry of Finance in developing and executing medium- to long term reforms," it said.
Harris will meet entrepreneurs, students, women and farmers while in Ghana and will also visit the historic Cape Coast Castle where slaves were kept 400 years ago.
The vice president also brought news of a new initiative against insurgents.
"To help address the threats of violent extremism and instability, today I am pleased to announce $100 million in support of Benin, Ghana, Guinea, Cote d'Ivoire and Togo," she said.
At their joint news conference, President Akufo-Addo reiterated that he was concerned about Russian-back mercenary Wagner Group's presence in West Africa.
"It raises the very real possibility ... that once again our continent is going to become the playground for great power conflict," he said, standing alongside Harris.
"The plan is intended to address regional threats of violent extremism and instability in Coastal West Africa," the vice president's office said in a statement.
Harris was asked during the news conference whether she would be promoting LGBT rights during her tour, including in Ghana where a bill that would severely restrict those rights is going through parliament.
"I have raised this issue," Harris said, adding that she felt very strongly about supporting freedom and equality for all people, and that LGBT rights were a human rights issue.
Ghana's draft bill would make it a crime to be gay, bisexual or transgender. Gay sex is already punishable by up to three years in prison under Ghanaian law, though no one has been prosecuted in years.
Akufo-Addo responded to a question about the bill from a U.S. reporter by saying that it was not official government policy but rather had been put forward by legislators acting in a private capacity.
"I have no doubt that the parliament of Ghana will show as it has done in the past ... its sensitivity to human rights issues as well as to the feelings of our population, and will come out with a responsible response to the proposed legislation."
After Ghana, she will travel on Wednesday to Dar es Salaam in Tanzania. Harris's trip also includes visits to Tanzania and Zambia
The vice president's travel is the latest move in deepening US engagement with a continent largely ignored under Republican Donald Trump - and long viewed in Washington as more of a problem area than an opportunity.
"President Biden and I have made clear the United States is strengthening our partnerships across the continent of Africa," she said during a joint news conference with Ghana's President Nana Akufo-Addo.
The tour is also part of Washington's pushback against growing Chinese and Russian involvement in Africa, with US officials promoting what they say is the more positive US message.
China is Ghana's biggest bilateral creditor with about $1.9 billion of debt. Ghana's finance ministry said last week it expected to secure financing assurances "very soon", following meetings in China.
This report was sourced from Reuters and Agence France-Presse.