The 33-year-old made 86 appearances for the four-time world champions.
"After some time reflecting, the moment has come for me to end my national team career and clear the way for the young generation," Rudiger said in a social media post.
Rudiger made his debut in 2014, a month before Germany won the World Cup, but was not included in the squad which travelled to Brazil.
The centre-back said he wanted to focus on his club side Real Madrid, where he is under contract for the remainder of the season.
"A new chapter begins for me now, in which I will focus entirely on my club," Rudiger said.
Born in Berlin, Rudiger came through the Borussia Dortmund and Stuttgart youth systems before moving to Roma and later Chelsea in 2017, where he won the 2021 Champions League.
He moved to Real in 2022 and won the Champions League and La Liga in 2024.
Rudiger's time in the heart of the German defence coincided with a poor decade for the traditional heavyweights.
Germany crashed out at the group stage at the 2018 and 2022 World Cups, before a last-32 exit at the hands of minnows Paraguay in 2026, Rudiger's last match in Germany colours.
"Even though the big title eluded us in recent tournaments and we had to endure some painful defeats, this time was an incredibly special chapter for me—one that will shape me forever," Rudiger continued.
His highlight at international level was winning the 2017 Confederations Cup.
Rudiger's time at Dortmund overlapped with new Germany coach Jurgen Klopp's tenure at the club, but the defender did not make a first-team appearance.