The trio were instrumental as Germany emerged as world champions for the fourth time during the 2014 FIFA World Cup staged in Brazil.
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However, Germany were surprisingly knocked out of the 2018 FIFA World Cup in Russia in the group stage.
Germany coach Joachim Loew in his quest to build a new side that would be able to compete again at the highest level has decided to exclude Jerome Boateng, Hummels, and Thomas Mueller from his plans.
"I thank Mats, Jerome and Thomas for the many successful, extraordinary and unique years we shared," Loew told the best-selling Bild newspaper on Tuesday.
"But in the national team it is now all about laying the foundations for the future. We want to give the team a new face. I am convinced that this is the right step."
Loew said he had travelled to Munich to inform the players.
With close to 250 internationals between them, Hummels (70 caps), Mueller (100) and Boateng (76) were part of the same generation.
Hummels and Boateng, both 30, played together in the 2009 Under-21 European championship triumph as Germany started to reap the first rewards of a major and sustained investment in youth players that had started seven years earlier.
They all graduated to the senior team and took part in the 2010 World Cup where Germany's youngest tournament team in 76 years reached the semi-finals with an exciting run that included wins over England and Argentina.
Mueller, 29, has scored 10 goals at World Cups, winning the golden boot in 2010. He was the second-top scorer four years later with another five goals.
The trio's international cycle was complete when Germany were crowned world champions in 2014, having also clinched an extraordinary 7-1 victory against Brazil in the last four.
"Thomas, Mats, and Jerome have achieved a lot until now for German football," Germany team manager Oliver Bierhoff told Bild.
"They will continue to do so for their club. I continue to feel very connected to them and am thankful for the time we spent together in the national team."