The announcement comes just over a month after the 2026 World Cup, where Messi guided Argentina to the final before they were beaten 1-0 by Spain.
In a glittering international career, the former Barcelona winger made 207 appearances, scored 125 goals and provided 68 assists.
"After the time that has passed since the final, and after giving it a lot of thought, I want to let everyone know that I am retiring from the National Team," Messi wrote on his Instagram.
"It was a decision that hurt - and still hurts deep down - but I understand that the time has come.
"I swear to you that I always gave it my all - not just in these last few years when we won everything, but before that too; I always fought and left everything on the field for this jersey, to bring you joy and make you feel proud to be Argentine through football."
The 39-year-old is a World Cup winner with Argentina after triumphing in Qata in 2022, where he won the Golden Ball award for the second time in his career - after also clinching the Player of the Tournament trophy in 2014.
Messi enjoyed immense success with La Albiceleste, particularly during his later career, returning from retirement ahead of the 2018 World Cup.
The legendary footballer helped his country to then win the 2021 and 2024 Copa America tournaments, as well as the previously mentioned 2022 World Cup.
"Time is running short, chapters come to a close, and this is one that hurts me deeply. I love, have loved, and will always love being part of the National Team.
"I’ve given everything I had; I have nothing left to give, and besides, there are some great young players coming up who deserve to be here.
"Thank you for all the affection over these past 20 years. I will miss hearing you from the pitch so much. Now I’ll be just one of you, cheering and supporting from the outside (through the good times and the bad - especially the bad)."
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