Emmanuel began her acting career appearing in theatre in the late 1990s, acquiring roles in various West End productions such as the musical The Lion King.

[5][6] In an interview with the New York Daily News, she commented, "When I was 3, [I'd] always cause drama that my mum decided maybe I should channel it properly—so she started me on acting, singing and dancing classes".

[8][9][10] In January 2012, Emmanuel presented BBC Three's Websex: What's the Harm?, investigating the online sexual habits of 16–24 year olds in the UK.

[12][13] The following year, she was cast as Missandei, Daenerys Targaryen's interpreter, in HBO's fantasy drama series Game of Thrones.

[10] In an interview with Jimmy Kimmel, she confirmed that she received the news about winning the role when she was working in a clothes store as a shop assistant.

[15] Missandei was the only prominent character that was a woman of colour in the show, and her death scene, which took place whilst she was in chains, was unpopular among fans, being called an example of fridging and evoking an image of slavery.

That's how they’re going to do the only woman of colour?’Also in 2015, she played computer hacker Ramsey in the action film Furious 7,[19] and Harriet in the science fiction adventure Maze Runner: The Scorch Trials.