Since being beaten from the spot by Samuel Eto'o at the 2008 Africa Cup of Nations, he has saved every penalty he has been presented with while playing for Zambia. He has been the first-choice goalkeeper for Zambia since making his debut in 2004 and was a participant at the 2006 African Nations Cup, 2008 African Nations Cup, 2010 African Nations Cup and the 2012 African Nations Cup. On 12 February 2012, Mweene kept a clean sheet during the 2012 Africa Cup of Nations Final and saved one penalty kick (as well as successfully converted his own) in the shootout to decide the game, which was eventually won by Zambia. He was chosen as the goalkeeper of the tournament. During the 2013 Africa Cup of Nations Mweene converted a penalty kick, earning a 1–1 draw against Nigeria and also saved two penalties during the tournament.