Born in Budapest, Hungary, as Ferenc Hoffmann, he studied sculpture and painting, and then began publishing humourous essays and writing for the stage. He emigrated to Israel in 1949, where an immigration officer gave him the name Ephraim Kishon.
Acquiring a mastery of Hebrew with remarkable speed, he started a regular satirical column in the easy-Hebrew daily, Omer, after only two years in the country. From 1952, he wrote the column "Had Gadya" in the daily Ma'ariv. Devoted largely to political and social satire but including essays of pure humour, it became one of the most popular columns in the country. His extraordinary inventiveness, both in the use of language and the creation of character, was applied also to the writing of innumerable sketches for theatrical revues. His full-length play, Ha-Ketubbah, "The Marriage Contract," had one of the longest runs in the Israel Theater, while his feature films, Sallah Shabbati and Blaumilch Canal, which he wrote, directed, and produced, enjoyed international distribution. His sketches and plays have been performed, in translation, on the stages and television networks of several countries. Collections of his humourous writings have appeared in Hebrew and in translation, the English translations including Look Back Mrs. Lot (1960), Noah's Ark, Tourist Class (1962), The Seasick Whale (1965), and two books on the Six-Day War and its aftermath, So Sorry We Won (1967), and Woe to the Victors (1969). Two collections of his plays have also appeared in Hebrew, Shemo Holekh Lefanav (1953) and Ma´arkhonim (1959).
Divorcing his first wife Eva (Chawa) Klamer, he married his second wife Sara (née Lipovitz) in 1959, who passed away in 2002. He has three children: Raphael (b. 1957), Amir (b. 1964), and Renana (b. 1968). In 2003 he married Lisa Witasek.