He was appointed as the Head coach of the Ghanaian national team in April 2012, describing himself as "the underdog" in the process. His Ghana team qualified for the 2014 World Cup in Brazil, making him the first black African coach to take the country to the World Cup. He was given a new two-year contract in May 2014. After the country exited the World Cup in the group stages, Appiah defended his team.
He left his position as Ghana manager by mutual consent in September 2014.