The West Bromwich Albion player made 44 appearances for his country and netted five goals including a memorable strike against Belgium in the Euro 2016 quarter-finals.
The Dragons failed to qualify for the World Cup in Russia this summer, and Robson-Kanu has now decided to step down from the international set-up at the age of 29.
"I have made the decision to retire from international football," Robson-Kanu told reporters.
"Long thought, but a decision made; commitments to my family and dedicating what time I have available to them and choosing to focus on my club career within sport and time needed away from the game.
"I wish Ryan Giggs and the team continued success in the years to come, and appreciate his understanding and support, a new generation to continue building on what Gary Speed and Chris Coleman have set in place."
Wales host Ireland at the Cardiff City Stadium on September 6 before visiting Denmark on September 9.