Guzan made his United States national team on February 19, 2006 in a friendly 4–0 win over Guatemala in Frisco, Texas. He played the first 80 minutes before being replaced by fellow debutant Zach Wells. He was a non-playing member of the side that won the 2007 CONCACAF Gold Cup. He was called up for the 2007 Copa América in Venezuela, where he played in a 1–0 loss to Colombia for his next cap on July 5.