Cosmatos was born to a Greek family in Florence, Italy, and grew up in Egypt and Cyprus.[1] He is said to have spoken six languages.[2] After studying film at the London Film School, where he met his future wife, Swedish sculptor and artist Birgitta Ljungberg, when they both were 17, he became assistant director to Otto Preminger on Exodus (1960), based on Leon Uris's novel about the birth of Israel.[1] In 1960, he married Birgitta, born in Haverö, Ånge municipality in Medelpad, 26 July 1941. Thereafter he worked on Zorba the Greek (1964), in which Cosmatos had a small part as Boy with Acne. On 1 Feb. 1974, the couple had their first and only child, Panos Cosmatos, born in Rome. In the early 1980s, the family moved to Victoria, British Columbia.
Late in his career, Cosmatos received more praise for Tombstone, a 1993 Western movie about Doc Holliday and Wyatt Earp. This film was particularly praised for the exceptional performance of Val Kilmer as Doc Holliday. Kurt Russell, who played Wyatt Earp, said Stallone recommended Cosmatos to him after the removal of the first director, writer Kevin Jarre, but Cosmatos had also worked with Tombstone executive producer Andrew G. Vajna before on Rambo: First Blood Part II.
On 6 July 1997, his wife Birgitta died (she is buried where she was born), and Cosmatos' career came to a halt. Outside of his film career, Cosmatos was a collector of rare books, focusing mainly on 19th–20th Century English literature and signed & inscribed works. His library was sold through Sotheby's.[5]