Cosmatos was born to a Greek family in Florence, Italy, and grew up in Egypt and Cyprus. He is said to have spoken six languages. After studying film at the London Film School, he became assistant Director to Otto Preminger on Exodus (1960), based on Leon Uris's novel about the birth of Israel. Thereafter he worked on Zorba the Greek (1964), in which Cosmatos had a small part as Boy with Acne.
Cosmatos found success in Italy for directing the films Rappresaglia (1973) with Marcello Mastroianni and The Cassandra Crossing (1976) with Sophia Loren. In 1979, he made the successful British World War II adventure movie Escape to Athena, starring an all-star ensemble cast including Roger Moore, David Niven, Telly Savalas, Elliott Gould and Claudia Cardinale. He made his North American directorial debut with the Canadian horror film Of Unknown Origin. He then directed the box-office hit Rambo: First Blood Part II starring Sylvester Stallone, and Cobra, another successful Stallone vehicle, in 1986. In 1989 he directed the science-fiction horror film Leviathan, starring Peter Weller, Richard Crenna, Ernie Hudson, and Amanda Pays, with special effects designed by Stan Winston.
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.
George P. Cosmatos died of lung cancer on 19 April 2005, at his home in Victoria, British Columbia at the age of 64. He was survived by one son, Panos Cosmatos, who directed the independently released surreal film Beyond the Black Rainbow. Panos claims that his film was funded primarily by royalties from his father's film, Tombstone.
Outside of his film career, Cosmatos was a notable collector of rare books, focussing mainly on 19th-20th Century English literature and signed & inscribed works. His library was sold through Sotheby's.
