Black Stars head coach CK Akonnor has made four changes to the team that drew with South Africa on Thursday.
Arsenal Midfielder Thomas Partey has been handed a starting role in the midfield ahead of Afriyie Acquah.
Captain Andre Ayew and Jordan Ayew have both been named in the starting eleven.
Former Asante Kotoko forward Kwame Opoku has also been dropped for Gent forward Osman Bukari who came on in the second half against South Africa.
He maintained his backline of Razak Abalora, Benson Anang, Abdul Ganiyu, Nicholas Opoku and Baba Rahman.
Full starting XI
17.Baba Abdul Rahaman
A win against Sao Tome and Principe will mean Ghana will top Group C with 13 points.
By Francis Hema|3news.com|Ghana