She began her career acting in short films and received recognition playing Max Fox in the FX comedy series Better Things (2016–2022).

Madison rose to prominence with her acclaimed performance as the title character in the romantic comedy-drama film Anora (2024), which earned her many accolades, including the BAFTA Award for Best Actress and Best Actress nominations from the Golden Globes, Screen Actors Guild and the Academy Awards.

[10][11] In 2016, Madison began a starring role as Max Fox in the FX comedy-drama series Better Things created by Louis C.K.

[15][16] Madison earned recognition for her role as the Manson Family member Susan "Sadie" Atkins in Quentin Tarantino's period drama film Once Upon a Time in Hollywood,[17][18] which premiered at the 2019 Cannes Film Festival and was a commercial success with a worldwide gross of $374.3 million.

[28] She was cast by Sean Baker in the romantic drama film Anora as the titular stripper and sex worker.

[34][35] Richard Lawson of Vanity Fair praised Madison's Brooklyn accent saying her performance was "big and vivid, brash but charming".