He was arguably the most famous Abkhaz writer, renowned in the former Soviet Union for his vivid descriptions of Caucasian life, mostly written in Russian. He has written various stories, most famously "Zashita Chika", which star a crafty and likable young boy named "Chik".

The most famous intellectual of Abkhazia, he distanced himself from the Abkhaz secessionist strivings in the late 1980s and criticised both Georgian and Abkhaz communities of Abkhazia for their ethnic prejudices. He warned that Abkhazia could become a new Nagorno-Karabakh.

He was probably best known in the English speaking world for Sandro of Chegem, a picaresque novel that recounts life in a fictional Abkhaz village from the early years of the 20th century until the 1970s, which evoked praise for the author as "an Abkhazian Mark Twain." Mr. Iskander's humor, like Mark Twain's, has a tendency to sneak up on you instead of hitting you over the head. This rambling, amusing and ironic work has been considered as an example of magic realism, although Iskander himself said he "did not care for Latin American magic realism in general". A section of the novel dealing with Sandro's encounter with Joseph Stalin was made into the Russian film Baltazar's Feasts, or a Night with Stalin in 1989.

Iskander lived in Moscow and was a writer for the newspaper Kultura.

"Of all the writers in the USSR, Fazil Iskander (born 1929) is surely the one whose works can best survive translation and cultural export. One can easily imagine him becoming a best seller in this country. This is somewhat paradoxical, because, though he writes in Russian, Iskander comes from a tiny nation that few Americans have ever heard of—Abkhazia. This so-called republic lies beside Georgia on the Black Sea. As the world will discover sooner or later, Iskander is the Gabriel García Márquez of Abkhazia. The major work of Iskander's life is a novel called Sandro of Chegem. In a series of semi-independent tales, Iskander tells the 80-year story of Uncle Sandro from the 1880s to the 1960s—and Sandro's story is also the story of the Abkhazian people, with all their customs, superstitions, passions, and sufferings. In Iskander's case regionalism is not a barrier to understanding, because there is an epic, universal quality to his writings.…"

—Carl R. Proffer, The New Republic