The Prince of Wales will talk about the "indelible mark" left by slavery in world history and will recognize the role the UK has had to play.
Ghanaian President Nana Akufo-Addo has invited Prince Charles to speak at the International Conference Center in Accra on Monday, where he will speak extensively about the important role that Ghana plays in the Commonwealth.
He is expected to say, "The history of our two nations is closely linked, and although we have a common chance today, we can never forget that our past has sometimes been witness to tragedies and loss and sometimes grave injustice.
"The terrible cruelty of the slave trade and the unimaginable suffering it caused left an indelible mark on the history of the world."
He will recognize Britain's leading role in abolishing the slave trade, but he will strengthen the responsibility of the United Kingdom to ensure that cruelty is never forgotten.
The prince is expected to say, "While Britain can be proud that it later led to the abolition of this shameful trade, we have a shared responsibility to ensure that the cruel horror of slavery is never forgotten and that we have the Existence does not abhor modern slavery, and that we staunchly promote and defend the values that today become incomprehensible to most of us, that humans can ever treat with such extreme inhumanity.
"Yesterday at Osu Castle, it was particularly important to me – I had my first visit there forty-four years ago – that I should acknowledge the most painful chapter in Ghana's relations with the nations of Europe, including the United Kingdom. "
The prince visited Osu Castle, also known as Fort Christiansborg, to see the place where over 1.5 million African slaves were housed and processed during the history of the slave trade.
The fort was built in 1661 by the Danes and served as a keep before ointments were sent to the New World.
It later became the headquarters of the British colonial government until Ghana gained official independence from Great Britain in March 1957.
Prince Charles was seen leading the castle's spiral staircase down to the beach, the last passage slaves used before being loaded onto ships.
At the conference on Monday, the prince will also use his address to praise the bilateral relations between Ghana and the United Kingdom and to underline the importance of the Commonwealth in overcoming some of the world's most pressing issues.
He will say, "The Commonwealth should seek a renewed relevance to the lives of its citizens and rely on its unparalleled network of expertise to provide practical solutions to some of the most urgent challenges of our time, many of which are ever deeper and deeply integrated.
"No topic is more urgent than that of climate change."
The Duke and Duchess of Cornwall will complete their Africa tour with a visit to Nigeria from 6 to 8 November.