At the international level, Afful made his Ghanaian debut at the 2008 Africa Cup of Nations, helping Ghana to a third-place finish at that tournament. He appeared for the Black Stars at four more AFCON tournaments, finishing as runners-up in 2010 and 2015. He was called up to Ghana's squad for the 2014 FIFA World Cup, appearing twice during the tournament. Afful captained his nation for the first time in a friendly against Congo on 1 September 2015.