Edgar Ramirez started acting in his native Venezuela, where he appeared in soap operas after switching his career from journalism to performing. His first mainstream, international success as an actor came from his supporting performance as the assassin Paz for Operation Blackbriar in the third Jason Bourne film, "The Bourne Ultimatum," in 2007. Although he has limited screen time in the film, his villainous role in the movie stands out.

In a 2007 interview with El Universal, the actor was asked why he found the part of Paz and his experience working on the film to be stimulating. He answered, "It is a character study, of which there are many variables. But Paul Greengrass, the director, always defends the integrity of the movie, and that it has to be as good or better than its predecessors. That is very stimulating."

He then added how it was a fulfilling experience since his discussions with Greengrass and Matt Damon (Jason Bourne) benefited his performance. He brought the same intensity he captured with Paz to his next featured part, as the Greek deity Ares in 2012's "Wrath of the Titans." But his next significant role would find the actor portraying the passionate fashion designer Gianni Versace in Ryan Murphy's "American Crime Story" series.