The 35-year-old represented Australia in 2022 World Cup in Qatar, scoring a headed goal against Tunisia that secured the country's first World Cup victory in 12 years.
Duke also played a key role in helping Australia's qualification campaign for the 2026 World Cup, scoring the winner against Saudi Arabia in the qualifiers last year. However, he missed out on the final squad selection for the tournament in North America.
"After a lot of reflection, the time has come for me to officially announce my retirement from international football," Duke said in a statement on Saturday.
"As a kid growing up in Australia, I dreamed of wearing the green and gold just once. To have gone on to represent my country 50 times is a dream come true 50 times over, and a privilege I never took for granted.
"While I will cherish every memory, scoring for Australia at the 2022 FIFA World Cup remains the absolute highlight of my career. It has been the greatest honour of my life to pull on the Socceroos jersey and represent our nation."