After debuting in 1984 with the controversial single »Lemon Incest” (a duet with her father) and a role in the film Paroles et Musique alongside Catherine Deneuve, Gainsbourg spent the next couple of decades focusing on acting, onscreen as well as onstage. Her extensive filmography includes Michel Gondry's The Science of Sleep and Todd Haynes' Bob Dylan biopic I'm Not There, and in 2009, she was given the award for Best Actress at the Cannes Film Festival for Antichrist. She re-teamed with director Lars von Trier for Melancholia and Nymphomaniac.

Gainsbourg reignited her musical aspirations in 2006 with the critically acclaimed record 5:55, produced by Nigel Godrich and boasting contributions by Air and Jarvis Cocker. For her follow-up album, IRM, she worked closely with Beck. She returned with her fourth proper artist album in 2017 with Rest, produced by SebastiAn and featuring collaborations with Paul McCartney and Guy-Manuel de Homem-Christo of Daft Punk. Most recently, Gainsbourg was a featured guest on the album Peradam by Patti Smith and Soundwalk Collective and on Glowing in the Dark by London electro-rockers Django Django.