De Armas made her acting debut in 2006, portraying the role of Marie on Una rosa de Francia. At the age of 18, she moved to Spain. Her first major television success there was the Spanish TV series El Internado, in which she starred as Carolina Leal, airing on Antena 3 in 2007. She continued her career in the film Mentiras y gordas (2009), the TV series Hispania, la leyenda (2010–2012), and Blind Alley (2011).
In 2014, de Armas moved to Los Angeles. She appeared in the film Por un puñado de besos. In 2015, she starred in Knock Knock, alongside Keanu Reeves, whom she also co-starred with in the 2016 film Exposed. She credits Hands of Stone director Jonathan Jakubowicz as having "discovered her", since he gave her first international role, in the 2016 release. Staying busy through 2016, she also had a prominent role in War Dogs, playing the moral wife of Miles Teller's character.
In 2017 she appeared in Overdrive, a French action-thriller film, and Blade Runner 2049 in the role of Joi, a holographic computer program which is the main character's girlfriend. Her performance in the film received high praise and has been characterized as a breakout role.
In 2019, Armas starred in the action crime film The Informer, directed by Andrea Di Stefano, opposite Rosamund Pike and Joel Kinnaman. She next starred in Wasp Network directed by Olivier Assayas, which had its world premiere at the Venice Film Festival on September 1, 2019. She then had a starring role in Knives Out, a Whodunit murder mystery film directed by Rian Johnson, opposite an ensemble cast including Daniel Craig, Jamie Lee Curtis, Christopher Plummer, Chris Evans, Toni Collette, Michael Shannon, and Katherine Langford. The film had its world premiere at the Toronto International Film Festival in September 2019, and received rave reviews from critics, who praised her performance. It was released on November 27, 2019, by Lionsgate.
In 2020, she will appear in No Time to Die, the next James Bond film reuniting her with Daniel Craig, directed by Cary Joji Fulcunaga. All of Armas’s scenes were written by Phoebe Waller-Bridge. She will also appear in the erotic thriller Deep Water, directed by Adrian Lyne, based upon the novel of the same name by Patricia Highsmith, opposite Ben Affleck. It is scheduled to be released on November 13, 2020, by 20th Century Fox.
She will next star in Blonde portraying the role of Marilyn Monroe, directed by Andrew Dominik for Netflix, the crime drama film The Night Clerk, opposite Tye Sheridan, and in Sergio, directed by Greg Barker, also for Netflix
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