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After studying communications at the Andrés Bello Catholic University, Ramírez worked in media and considered becoming a diplomat. When filmmaker Guillermo Arriaga praised a short film he had done, he decided to pursue his performing hobby as a career.

Ramírez played a CIA assassin in the action-thriller film The Bourne Ultimatum (2007). His portrayal of Carlos the Jackal in the 2010 biopic television miniseries Carlos won him the César Award for Most Promising Actor and nominations for a Golden Globe and Emmy Award for Best Actor. He then played a CIA operative in Zero Dark Thirty (2012), and boxer Roberto Durán in the biographical sports film Hands of Stone (2016).

Ramírez received several accolades for his portrayal of Gianni Versace in the 2018 miniseries The Assassination of Gianni Versace: American Crime Story. In 2020, he had a recurring role in the HBO miniseries The Undoing. In 2022, Ramírez was part of the Un Certain Regard jury at the Cannes Film Festival.