The 36-year-old was part of the Irish squad that failed to win a game at this summer's European Championships in Poland and Ukraine.
However, following weeks of consideration, Given has now decided to concentrate on his club career with Aston Villa.
"After a lot of thought and consideration, I have made the most difficult decision to retire from international football," he wrote on Twitter. "It's been a great honour and privilege to play and on occasion captain the team.
"I shall remain a huge fan of the team as I have been all my life and I wish them every success for the future. I wish to thank all the players, managers, staff and most importantly the most wonderful fans in the world.
"Finally I would like to thank my wife Jane, my two amazing kids and my entire family for their unwavering support over the 16 years and 125 caps."
Given made his international debut in March 1996 against Russia.