Estudiantes LP Ascacíbar arrived at
Estudiantes (LP) in 2006 at the age of 8, after performing a trial in which coach Omar Rulli –father of
goalkeeper Gerónimo Rulli – was surprised by his tenacity, describing Ascacíbar as "a fan of practice, very obsessive from a young age to improve his technique, as well as with his daily work". Denoting his skill as a
central midfielder from early on, and a strong presence on the pitch rarely seen among academy players,
Rusito ("The Little Russian"), as he was nicknamed since childhood due to his blond hair and blue eyes, quickly became a key player in his age class. After recording impressive performances in his first four years in
AFA youth divisions, the team's youth football coordinator Hermes Desio promoted him to the reserves for the first time in late 2014, and Ascacíbar made his debut in a match against the reserves of
Rosario Central away at the
Estadio Gigante de Arroyito. That same year, and on the recommendation of former international
Juan Sebastián Verón who was now president of the club, Ascacíbar finished his secondary studies at the Colegio de Estudiantes and enrolled in
Anthropology at the
National University of La Plata, On 8 February 2016, Ascacíbar made his professional debut for Estudiantes, playing the entire match against
Lanús in the
Argentine Primera División which ended in a 1–0 loss. Over the course of the season, his performances with the first team improved and he became a starter for the team. In his first full season as a first-team player, he appeared in all games and was the player who recovered the most balls. At the end of the season, he was awarded the
Olimpia Award in the category Best Player of Local Football. His final appearance for the club came on 3 August 2017 in a 2–0 victory against
Nacional Potosí in the
Copa Sudamericana. When he was subbed off, he received a standing ovation at the
Estadio Ciudad de La Plata.
VfB Stuttgart On 22 August 2017, Ascacíbar signed a five-year deal with
VfB Stuttgart. He made his debut on 10 September, coming off the bench in the 62nd minute for
Orel Mangala in a 3–1 away defeat against
Schalke 04. In August 2018, Ascacíbar extended his contract with Stuttgart until June 2023. At the end of the season, the club suffered relegation to the
2. Bundesliga. He scored his first goal for Stuttgart against
Dynamo Dresden on 3 November 2019 in the 2. Bundesliga, slotting home from short distance in an eventual 3–1 victory at
Mercedes-Benz Arena. This came after a period, where Ascacíbar had been suspended by the team due to his demands of being the starting
defensive midfielder. Manager
Tim Walter afterwards called him a "temperamental boy" who could sometimes "get carried away".
Hertha BSC On 1 January 2020, Ascacíbar signed a long-term contract with Bundesliga club
Hertha BSC. He made his debut for the club on 19 January in a 4–0 home loss to
Bayern Munich. Despite the defeat, Hertha manager
Jürgen Klinsmann praised Ascacíbar, calling him "one of the best
Number 6 in the Bundesliga". In May 2020, however, following the upheaval of the
COVID-19 suspension of German football, he suffered a foot injury that kept him out for several weeks. Several injuries would keep him sidelined the following months, and he failed to make any more appearances in 2020. Ascacíbar returned to the pitch on 30 January 2021 under new manager
Pál Dárdai, playing 89 minutes of the 3–1 defeat to
Eintracht Frankfurt. In a
Berliner Derby against
Union Berlin on 4 April, Ascacíbar was shown a yellow card after a verbal altercation with opposing player
Nico Schlotterbeck, which prompted a subsequent investigation by the
German Football Association (DFB). The investigation was, however, discontinued on 8 April after the conditions for blatantly anti-sports conduct were not met. In the following game, on 10 April, Ascacíbar was also the centre of attention. Despite scoring the opening goal against
Borussia Mönchengladbach in an eventual 2–2 draw, he
sneered when substituted off in the second half, which coach Dárdai criticised afterwards. Ahead of the
2021–22 season, in a pre-season friendly against
Liverpool, Ascacíbar suffered a
concussion after colliding with opposing goalkeeper
Caoimhín Kelleher after scoring the opening goal in a 4–3 victory. He returned to the pitch for the first competitive game of the season, playing the entire
DFB-Pokal match against
SV Meppen.
Loan to Cremonese On 23 July 2022, Ascacíbar joined
Serie A club
Cremonese on loan with an option to buy. On 14 August he made his debut for the club in Cremonese's 3–2 Serie A loss to
Fiorentina.
Return to Estudiantes On 18 January 2023, Ascacíbar returned to
Estudiantes on loan. On 26 May 2023, Hertha announced that the transfer was made permanent.
Boca Juniors On 27 January 2026, Ascacíbar joined
Boca Juniors, signing a four-year contract. Boca purchased 80% of his rights from Estudiantes. ==International career==