After appearing in the television sequel Mean Girls 2 and the first two seasons of Pretty Little Liars (both 2011), she had her breakthrough playing Rebekah Mikaelson in the CW supernatural drama series The Vampire Diaries (2011–2014), The Originals (2013–2018) and Legacies (2021–2022).

In film, Holt starred in the comedy drama Blue Like Jazz (2012) and the survival thriller 47 Meters Down (2017) to positive critical reception, followed by roles in a series of less-well-received projects, and later in the acclaimed comedy horror film Untitled Horror Movie (2021).

[3] In 2005, Holt won the role of Emma Gilbert in the Network Ten children's television show H2O: Just Add Water.

Starring alongside Norman Reedus and Heather Stephens, the film was released 21 July 2009 straight-to-DVD.

In addition to television and film roles, Holt has appeared in advertisements for Dreamworld, Sizzler, and Queensland Lifesaving.

[5] On 13 January 2013, The CW announced that Holt had joined the cast for the backdoor pilot of The Vampire Diaries spin-off The Originals, where she reprised her role as Rebekah Mikaelson.

[12] Also that year, Holt starred as Kate in the underwater survival horror film 47 Meters Down, opposite Mandy Moore and Matthew Modine, which was released in theaters on 16 June 2017.

[19] In January 2023, Holt announced that she had opened a website, in which weekly she would bring content to her fans such as make-up, fashion choices, maternity issues and much more.

[20] In November 2022, Holt decided to run the New York City Marathon to donate her fee to Boston Children's Hospital for a total of $162,000.