Appiah, who managed the Black Stars between 2012 and 2014, has been handed a two-year contract and will start his duties on May 1.
He takes over from Avram Grant, who resigned in February after two-and-a-half years in charge.
The Ghana Football Association said in a statement: 'The Ghana Football Association (GFA) has named James Kwesi Appiah as the new coach of Senior National Team, the Black Stars.
'The decision was taken by the Executive Committee of the GFA on Tuesday after approving the report of the six-man coaching search committee.
'Appiah will be handed a two-year contract and will start his duties on 1st May, 2017.
'He will also take full charge of the Local Black Stars.'