Leonie Benesch was born on April 22, 1991 in Hamburg where she spent the first four years of her life. She first went to school in Tübingen, where she lived with her family for five years and attended the Freie Waldorfschule, and later she attended the Rudolf Steiner Schule in Bielefeld-Schildesche. By her own account, there was no television in her family home, but when her father bought a laptop, she began to buy DVDs and was particularly fascinated by the behind-the-scenes bonus material that gave an insight into the making of the film.     

Having already performed in school plays and a children's circus, in 2006 she had a small supporting role in Martin Theo Krieger's film about neglected teens, "Beautiful Bitch," which premiered at the Berlin Film Festival. In 2008, at the age of 17 and still a high school student, she played a nanny in one of the lead roles in Michael Haneke's award-winning drama "Das weiße Band" ("The White Ribbon"). Her performance in the film not only brought her increased attention from audiences and the industry, but also earned her the New Faces Award in 2010. This success encouraged Benesch to move to Berlin after her high school graduation, where she took acting classes with Mike Bernardin from the UK.

Appearances in the movies "Picco" as the girlfriend of Constantin von Jascheroff's main character and "Satte Farben vor Schwarz" ("Colours in the Dark", both 2010) with Senta Berger and Bruno Ganz followed. She also appeared in two short films, one episode each of the TV crime series "SOKO Köln" and "Der Kriminalist" as well as in the biopic "George" about the actor Heinrich George and in the TV thriller "Freunde bis zum Tod" from the hugely popular and long-running series "Tatort" (both 2013).

Inspired by Mike Bernardin, Benesch began studying acting in 2013 at the prestigious Guildhall School of Music and Drama in London, which accepts only about 30 students out of 3,000 applicants each year. After continuing to work in front of the camera for film, television, and streaming productions throughout her studies, she successfully graduated in 2016. Her work during her studies includes the TV adaptation of Siegfried Lenz's short story "Die Flut ist pünktlich" alongside Ina Weisse, August Zirner, Jürgen Vogel and Nicolette Krebitz, and especially the hit series "Babylon Berlin", where she played Greta Overbeck for three seasons until 2020. This performance earned her the German Actor's Award and brought her to the attention of a wider audience.

Further series appearances after her studies included guest roles in the popular British series "Howards End" and as Prince Philip's sister in "The Crown" (both 2017), as well as in the German series "Morden im Norden" (2018) and in the Netflix miniseries and family story "Die Zeit der Geheimnisse" ("Holiday Secrets", 2019) with Corinna Harfouch and Christiane Paul. She took on one of the lead roles in Uli Edel's multi-part TV film "Der Club der singenden Metzger" ("The Master Butcher", 2019), about two families who emigrate from Germany to the USA after the First World War.   

Based on the story "Erfindung einer Sprache" by Wolfgang Kohlhaase, the German-Russian-Belarusian drama "Persischstunden" ("Persian Lessons") premiered in 2020, in which she appeared alongside Nahuel Pérez Biscayart and Lars Eidinger in a supporting role.   

Also in 2020, she had an important role in the German-American series "Spy City," set in Berlin and London during the Cold War. In 2021, she starred alongside David Tennant in the British adaptation of Jule Verne's "Around the World in 80 Days". She was selected as German 'European Shooting Star 2023' by the jury of the European Film Fund in December 2022.    

Ilker Çatak's "Das Lehrerzimmer" ("The Teachers’ Lounge") premiered in the Panorama section of the Berlinale 2023, with Leonie Benesch in the highly acclaimed lead role of an idealistic teacher who finds herself in a moral dilemma when a series of thefts occur at her school. For this film, she was nominated for the German Film Award as Best actress in a leading role.   

After a leading role in the underwhelming Frank Schätzing adaptation "Der Schwarm" ("The Swarm," DE/FR/IT 2023, TV), Benesch appeared as a reporter in a leading role in the feature film "September 5" (DE/US 2024), which focuses on the 1972 Munich Olympics attack. In 2024, Benesch worked on two film productions: she played the title role in Petra Biondina Volpe’s nurse drama "Heldin" (CH/DE) and took on a supporting role in Wolfgang Becker’s final film, "Der Held vom Bahnhof Friedrichstraße" (both set to premiere in 2025).