Cilenti was born in Bradford, to Italian parents from Benevento. He worked with his girlfriend, Actress Sienna Guillory, in the 2001 film Late Night Shopping. The two were married in 2002, and they have continued to appear together in various works. In February 2011 Guillory gave birth to their twin daughters, Valentina and Lucia, named after Guillory's grandmother and great aunt, who were also twin sisters.
He also performed at The Royal Court in a series of plays written and directed by Russian artists entirely in Russian; in Thai ballet as Orpheus in Backpacker Orpheus, a play devised entirely from people's experiences in the 2004 Indian Ocean earthquake; and in conceptual theatre for new-writing company Paines Plough in a series of shows (including a one-man show) commissioned over a number of seasons by Miuccia Prada to showcase collections for her Miu Miu line at Milan Fashion Week.
In 2007, Cilenti had a recurring role in the CBS series NCIS as terrorist Mamoun Sharif.
His first novel, Mediterranean Homesick Blues, co-written with Ben Chatfield, was published in 2012.
Enzo appeared in Kick-Ass 2 (2013) and Guardians of the Galaxy (2014). In The Theory of Everything, he portrayed Astrophysicist Kip Thorne.
In 2015 he joined the cast of the HBO series Game of Thrones in Season 5 as Yezzan zo Qaggaz, and he also appears in the BBC series Jonathan Strange & Mr Norrell in the role of Childermass.
Cilenti played the part of Aubrey Hackett in the Amazon Studios series The Last Tycoon, which was released in July 2017.
