The second leg of her trip will take her to the Cape Coast castle.
The two first ladies than traveled to Jubilee House, Ghana's presidential palace, for a private meeting.
The visit, alongside Ghana's First Lady Rebecca Akufo-Addo, to Accra's Ridge Hospital set the tone for the trip as a whole.
It also portrays Trump as a first lady who is passionate about serious issues.
The visit is being organised in partnership with the United States Aid Agency (USAID) and will involve the four countries, described by Mrs Trump as "four lovely and very different countries in Africa", who have worked closely with the USAID in various areas.
(Carlo Allegri/Reuters) Dancers greet US first lady Melania Trump on arrival in Accra, Ghana, as she begins her tour of several African countries, on October 2, 2018.
"No one knew who the message was intended for, leaving it - and her - up for interpretation". She later joined Akufo-Addo for tea.
"She is interested in Africa because she has never been there before", her communications director Stephanie Grisham said. "This is her trip, her initiative", she said.
The trip to Africa works for the Trump administration on multiple levels, a source told Fox News. "Africa is so handsome, the most attractive part of the world, in many ways", he added.
"We are taking off for Africa!" she gushed.
Melania Trump's visit to Ghana will inevitably draw comparisons to when former president Barack Obama and his wife Michelle visited Ghana in 2009.