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.
In 2014 de Armas moved to Los Angeles. She appeared in the film Por un punado 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 the first international role in his Robert De Niro boxing epic which premiered in Cannes 2016.
Staying busy through 2016, in addition to Hands of Stone she had a prominent role in Todd Phillips' War Dogs, playing the moral wife of Miles Teller's character who sells weapons to the American government.
In 2017 she appeared in Overdrive, a French action-thriller film, in which she played Scott Eastwood's girlfriend who becomes involved in his plot to steal cars from a ruthless tycoon. While the film received scathing reviews, De Armas' performance received praise from critics.