Mensah was called up to the Ghana squad for the FIFA World Cup in Germany. He made his World Cup debut and started the whole game, in a 2–0 loss against Italy on 12 June 2006. Following a 2–0 win against Czech Republic, Mensah helped Ghana finished second place in Group E following a 2–1 victory over the United States in their final group match. After the final whistle, Mensah lifted his team jersey to reveal a T-shirt displaying "John Mensah – Rock of Gibraltar", his nickname in Ghana. However, in the round of 16, Ghana was eliminated by the defending champions, Brazil following a 3–0 loss. Ghana's head coach at the World Cup, Ratomir Dujković, would later cite Mensah for high commendations after the tournament.