In 2022, he was signed by Real Madrid, winning a Copa del Rey in his first season, as well as La Liga and a second Champions League title in 2024.

He was forced to miss UEFA Euro 2016 due to an injury suffered earlier in the season but he was part of the squad that won the 2017 FIFA Confederations Cup.

[8] Subsequently on 29 January 2012, Rüdiger made his Bundesliga debut for VfB Stuttgart's first team in a home professional match against Borussia Mönchengladbach, he was replaced by Raphael Holzhauser in the 79th minute of a 3–0 defeat.

[22] He made his debut on 6 August as a substitute replacing Marcos Alonso in the 79th minute in a 4–1 loss on penalties to Arsenal in the 2017 FA Community Shield.

[27] On 22 December 2019, Rüdiger made a complaint about racist abuse directed against him during the away match against Tottenham Hotspur, which received wide media coverage.

[32] On his 100th club appearance, he scored Chelsea's two goals, both headers assisted by Mason Mount in a 2–2 draw against Leicester City at the King Power Stadium on 1 February 2020.

[33] On 29 May 2021, Rüdiger won his first-ever UEFA Champions League after Chelsea beat Manchester City 1–0 in the final at the Estádio do Dragão.

[34] On 12 April 2022, he scored his first Champions League goal in a 3–2 away win over Real Madrid in the quarter-finals of the 2021–22 season; however, Chelsea were eliminated from the competition by losing 5–4 on aggregate.

[36] On 2 June 2022, Real Madrid announced that Rüdiger signed as a free agent for the club, penning a four-year deal starting with the 2022–23 season.

[41] On 11 October, he scored a header in the 95th minute against Shakhtar Donetsk in the Champions League group stage, which allowed his side to draw 1–1 and qualify for the knockout phase.

While jumping for the header, Rüdiger collided with Shakhtar goalkeeper Anatoliy Trubin and sustained a cut to the face that required 20 stitches.

[48] Although he was initially included in his nation's 23-man squad for UEFA Euro 2016, Rüdiger was later ruled out of the tournament due to injury, after tearing the anterior cruciate ligament in his right knee during a training session on 7 June.

[52] On 23 June, he was picked up for the second group stage match against Sweden as first choice centre-back Mats Hummels suffered an injury, the game ended 2–1 win for Germany.

[61] In 2015, ESPN described him as a "...tall, quick and athletic defender who is ... comfortable with the ball at his feet", also touting him as an "interesting prospect" who "...has all the necessary physical attributes to become a top-level centre-back.

[75] In March 2024, Rüdiger posted a photo of himself in a white ihram robe and on a prayer rug, with his index finger of his right hand pointing to the sky, with a greeting for Ramadan in the caption.

Former editor-in-chief of the Bild Zeitung, a German tabloid, Julian Reichelt commented on the athlete's tauhīd gesture claiming it was called the 'IS finger' by the Office for the Protection of Constitution and regarding as a sign of Islamism.

In response to this, the player agreed to an interview,[76] with the same tabloid, saying: "As a devout Muslim, I practice my faith, but I firmly distance myself from any kind of extremism and accusations of Islamism.