Schlotterbeck began his club career together with his older brotherKeven in his home districtRems-Murr atSG Weinstadt.[4] Both his father and uncleNiels Schlotterbeck used to play football themselves, although the former had to end his career early at the age of 19 due to illness.[5] During trial training sessions, the brothers Nico and Keven, who grew up in the districtBeutelsbach inWeinstadt, were accepted into the academy ofStuttgart Kickers. Their friendAntonios Papadopoulos, also born in 1999, was accepted along with them.[5] Papadopoulos and Schlotterbeck played together in Stuttgart until the Under-15s and also faced teams such asAjax Amsterdam andJuventus FC in junior tournaments.[5][6] After a year atVfR Aalen, which uncle Niels Schlotterbeck described as a ‘step backwards’,[6] things started looking up again for the youngster in 2015 when he was accepted into the Under-17s team ofKarlsruher SC.Under the coachLukas Kwasniok Schlotterbeck played as centre-back in that team and was together withTim Kircher for example part of the defense unit which would later go on to play professionally at the KSC.[7] As part of the Under-17s Schlotterbeck finished in the upper half of the league standings and scored two goals. Due to his rough playing style he was at risk for being suspended for too many yellow cards a second time after already receiving a first suspension during that season. At only 16 years old he was then called up into the Under-19 squad of the Karlsruher SC where he started, like in the previous Under-17s, as a regular. His first season in the Under-19 team was simultaneously his last at Karlsruhe. During that year he sometimes played midfield but overall he remained a steady part of the teams defense. Although playing as centre-back he still managed to score 7 goals, three of which were headers and provide one assist.
Together with his brother Keven, Schlotterbeck joined the Bundesliga side coached byChristian Streich in the summer of 2018. Both took part in the pre-season training and continued to train regularly with the first team afterwards.[8] Schlotterbeck debuted forSC Freiburg on 9 March 2019, coming on as a half-time substitute forPhilipp Lienhart in the 2–1 home win againstHertha BSC.[9] The two brothers started as central defenders on matchday 29 in a 2–1 away defeat inBremen, playing the full match alongsideDominique Heintz. They also played together frequently in theRegionalliga Südwest, where Nico scored two goals. While Keven spent the 2019−20 season on loan at newly promotedUnion Berlin, Streich focused on further integrating Nico into the first-team squad. Nico played the full 90 minutes in each of the first three league matches. In the 3–0 victory overMainz 05, he was rated by kicker as Freiburg’s second-best player in terms of average match ratings, behind goalkeeperAlexander Schwolow and alongsideLuca Waldschmidt andLucas Höler.[10] After a bad performance in Freiburg’s 2–1 loss against1.FC Köln on matchday 3 he was relegated to being a substitute in the following games.[10] For the remainder of the season, he only started one more game and was substituted on a few times, while also playing for the second team in thefourth division. Nevertheless, he received a call-up forGermany’s under-21’s.
In his final match for Freiburg in 2022, the club lost theDFB-Pokal Final on penalties but Schlotterbeck was awarded the man of the match.[11]
With his brother Keven returning from loan atUnion Berlin, they were in need of a new centre-back. They agreed a deal with Freiburg for a loan of Nico Schlotterbeck for the2020–2021 season.[12] He lived inKöpenick, in close proximity to his new club’s environment and started three of first four games of the season before being sidelined by a thigh injury until the second half of the season. Upon his return he proved to be a reliable centre-back, pushingFlorian Hübner to the bench. On matchday 22, he triumphed after a 1–0 win over his main club SC Freiburg where his brother Keven still played. Nico had previously missed the first leg due to an injury. At the end of the season, Union Berlin ranked fourth in fewest goals conceded (championsFC Bayern München were fifth). As seventh in the table they earned the right to participate in the qualifiers for the newly introducedUEFA Europa Conference League, thanks to the victory of runners-upBorussia Dortmund in theDFB-Pokal. Schlotterbeck was voted into the German soccer rankings for the first time at the end of the season, where he finished 18th in the national class. That placed him ahead ofBielefeld'sAmos Pieper and behindHertha BSC'sNiklas Stark.[13]
On 2 May 2022,Borussia Dortmund announced the signing of Schlotterbeck on a five-year deal, starting from the 2022–23 season.[14] He joined for a reported €25 million transfer fee.[15] He would almost win the league with Dortmund in his first season, but merely became runners-up due to goal difference. In the 2023–24 season, he achieved the highesttackling success rate in theBundesliga at 71%, in addition to winning possession over 240 times, he also played a crucial role in his club's qualification to theChampions League final alongside fellow centre-backMats Hummels.[16]
Schlotterbeck is the nephew of former professional footballerNiels Schlotterbeck, who played for Freiburg.[21] His older brother,Keven, is a professional footballer who plays for Bavarian sideFC Augsburg.[22] Schlotterbeck's cousin, Sandrine, appeared on the seventh series of the German edition ofLove Island in 2022.[23]