"This was my last game for Greece," the 37-year-old told reporters.
"We wanted to stay on another week or even longer but you can't change it now."
The midfielder, who had his biggest moment when he helped Greece surprisingly win European Championship in 2004, said he would move aside for younger players.
"The national team has grown up, younger players have won invaluable experiences. This is no small thing and as we helped the team come of age we hope it will continue to be as successful in the future."
The hard-working Karagounis, who scored 10 goals for Greece, made his first appearance in 1999 against El Salvador and went on to play in three European Championships as well as two World Cups.
He scored the opening goal in their successful Euro 2004 run against Portugal in the group stage but missed the final due to suspension. He also scored the winner against Russia at Euro 2008 that saw Greece advance to the semi-finals.
While he had lost his starting spot in recent years, Karagounis played the entire 120 minutes of their 5-3 shootout loss to the Central Americans after a 1-1 draw following extra-time, bringing down the curtian on his international career with another tireless performance.
- Sports & Recreation