During her tour on Wednesday, Melania Trump walked slowly with a guide through various wings, asking questions.
She called the castle "a special place". "The dungeons that I saw, it's really something that people should see and experience", she said after she was asked to reflect on the visit.
She stayed at the 17th-century structure on the Ghana coast for an hour during a guided tour by the museum's director.
US First Lady Melania Trump visited a hospital in Ghana's capital Accra on the first day of her Africa tour.
According to the Osabarima Kwesi Atta II even though first lady's visit is relatively short, he said her visit to the Emintsimadze palace was wonderful, impressive and colourful.
Mrs. Trump, who was born in Slovenia, is on her first visit to Africa, with a goal of highlighting child welfare on the continent.
Mrs. Trump met Ghanaian officials there, including Mrs. Akufo-Addo, whom she greeted with a smile and "thank you very much".
Trump also spent about 10 minutes inside the dungeons where slaves were held before walking through the "Door of No Return" to be taken across the Atlantic Ocean.
Donald Trump Mocks Christine Blasey Ford's Testimony At Mississippi Rally
He returned to the theme during a campaign rally in Tennessee, where he accused opposition Democrats of being motivated by politics.
"It's very emotional", the first lady said before departing.
The first lady's visit was a lower-key affair than Obama's visit as the first black USA president, and reminders of his visit with wife Michelle were prominent.
"It's really a tragedy", she said.
The first lady's visit to Ghana, Malawi, Kenya and Egypt has been seen as an attempt to carve her own path and emerge from her husband's shadow and his divisive presidency.
Trump also cradled an infant and declared the baby a "beautiful boy" as she handed him back to his mother.
The most surprising fashion repeat however was in March 2017, when Melania wore the same $3,000 Valentino dress two days in a row - first modeling it in the Oval Office, while supporting her husband as he signed a new bill aimed at encouraging women to pursue careers in science, technology, engineering and mathematics (STEM).
The US First Lady cuddled some babies at the hospital, before also donating a phototherapy machine, teddy bears and assorted baby items.
But unlike her predecessors, her visit will be followed closely to see if she can build bridges after the president reportedly dismissed Africa as a collection of "shithole countries".