Haenel began her career as a child actress, making her film debut with Les Diables (2002) at the age of 12, and quickly rose to prominence in the French entertainment industry as a teenager.

She received her first César Award nomination for her performance in Water Lilies (2007), which also marked the beginning of her long professional and personal relationship with director Céline Sciamma.

[14] Manohla Dargis of The New York Times highlighted Haenel's performance in an otherwise mixed review of the film, recognizing her as having "the makings of a real star".

[16] In 2012, she was nominated in the same category for House of Tolerance (2011),[17] a period film directed by Bertrand Bonello, in which she played a prostitute at an upscale Parisian brothel at the turn of the twentieth century.

Writing for The Village Voice, Melissa Anderson compared her performance to that of Isabelle Adjani's in the 1970s and '80s, and declared her a worthy successor to Deneuve in French cinema.

In the 2017 Robin Campillo film BPM (Beats per Minute), Haenel portrayed Sophie, a headstrong HIV/AIDS activist of the Paris chapter of ACT UP.

David Rooney of The Hollywood Reporter noted her performance as evoking the "classic screwball heroine", a departure from her usually more serious roles, and complimented her on the "grace and buoyancy" she brought to the character.

The New Yorker's Richard Brody took note of her chemistry with co-star Noémie Merlant and complimented the actresses for being "relentlessly graceful, endowed with physical aplomb, contemplative insight, and strong emotion".

[31] Since 2019, Haenel and co-star Ruth Vega Fernandez have prepared to perform director Gisèle Vienne's [fr] adaptation of Robert Walser's L'Etang (The Pond) for theatres in France and Switzerland.

Haenel's last project was to be The Empire, written and directed by Bruno Dumont, but she explained that she left the film as "it was a dark, sexist and racist world that was defended.

[36][37] In May 2023, Haenel announced her retirement from the film industry in a letter published on French magazine Télérama, citing "complacency" over those accused of being sexual predators, including Gérard Depardieu, Roman Polanski and Dominique Boutonnat [fr].

Haenel advocates for promoting an alternative model in theater creation and is dedicated to opposing gender violence and sexual assault against women and young girls.

She connects these issues to the fundamental concerns of Marxist radical feminism and actively participates in discussions on police violence, anti-colonialism, environmentalism, and the Israeli-Palestinian conflict.

"[42][43][44] In 2014, Haenel came out as a lesbian during her César award acceptance speech and acknowledged her relationship with director Céline Sciamma, whom she had met in 2007 when she was a teenager on the set of Water Lilies.

[49] In a November 2019 Mediapart interview, Haenel accused director Christophe Ruggia of sexually harassing her from the time she was 12 to 15 after casting her in his film Les Diables.

[13] Haenel's account was backed up by many people who had worked on the film and noted Ruggia's inappropriate behaviour towards her, along with letters he had written her at the time proclaiming his love for her.