Germany coach Joachim Low has told Boateng, Hummels & Muller he does not intend to select them again for the national team.
Boateng and Hummels are both 30, while Muller is 29, and the Bayern Munich trio, who have 246 caps between them, helped Germany win the 2014 World Cup.
But Germany suffered a group exit at the 2018 World Cup before being relegated in the Nations League.
Low said: “2019 is the year of the new start for the German national team.”
He added: “We want to give the team a new face and I am convinced that this is the right step.
“The young national players will have the space they need to fully develop, and now they have to take responsibility.”
The last Germany game in which Boateng, Hummels and Muller all played was the 3-0 Nations League defeat in the Netherlands on 13 October.
As a result of then being beaten by France three days later, Germany suffered six defeats in a calendar year for the first time and lost two consecutive competitive matches for the first time since 2000.
Muller, who is Germany’s ninth highest scorer with 38 goals, came off the bench to win his 100th cap in the team’s last game, a 2-2 Nations League draw at home to the Netherlands in November.
Germany’s next match is a friendly against Serbia in Wolfsburg on 20 March before their first Euro 2020 qualifier against the Netherlands four days later.
German FA president Reinhard Grindel added: “I welcome the fact that Jogi Low is now furthering the change of our national team. The start of qualifying for the Euro 2020 is the right time for personnel changes.”