Before the 2006 season began, Nathan participated in the 2006 World Baseball Classic as one of the 30 players selected for the Team USA roster. He played the first game, a 2–0 win against Mexico, striking out the side while allowing one hit. He also pitched the 4–3 victory against Japan, again throwing a shutout inning. Nathan went on to pitch the last game for the United States in the ninth inning against Mexico, again not allowing a run and striking out two.