After appearing in several independent films, she had her breakthrough starring as Hannah Baker in the Netflix television series 13 Reasons Why (2017–2018), which earned her a Golden Globe Award nomination.

In 2012 as a teenager, Langford attended a Lady Gaga concert, the Born This Way Ball, which inspired her to learn to play piano.

[17][20] In the same year, she trained at Nicholson's Academy of Screen Acting and portrayed the role of Juan Perón's mistress in its 2015 production of Evita.

[20][21] In 2016, after declining the offer from Western Australian Academy of Performing Arts, Langford auditioned for Will, a television series centred on the early life of William Shakespeare.

[24] Several critics lauded her performance as Baker; The Hollywood Reporter wrote: "Langford's heartbreaking openness makes you root for a fate you know isn't possible.

The actress' performance is full of dynamic range, setting it against Minnette's often more complicated task in differentiating between moods that mostly go from uncomfortable to gloomy to red-eyed, hygiene-starved despair.

[36] In 2020, she starred in the film Spontaneous, a well-reviewed, dark comedy for which she received a Critics' Choice Super Awards nomination for Best Actress in a Science Fiction/Fantasy Movie.

Set in a re-imagined Arthurian world, Langford portrays Nimue, a teenage girl destined to become the Lady of the Lake.

[41] On 23 September 2024, Langford made her stage debut, taking over as Sally Bowles in the West End musical Cabaret at the Kit Kat Club, playing at the Playhouse Theatre for 18 weeks.