Born into a middle-class Jewish family in Budapest, Hungary, as Ferenc Hoffmann (Hungarian Hoffmann Ferenc), Kishon studied sculpture and painting, and then began publishing humorous essays and writing for the stage.

During World War II the Nazis imprisoned him in several concentration camps. At one camp his chess talent helped him survive as the camp commandant was looking for an opponent. In another camp the Germans lined up the inmates shooting every tenth person, passing him by. He later wrote in his book The Scapegoat, "They made a mistake—they left one satirist alive." He managed to escape while being transported to the Sobibor death camp in Poland, and hid the remainder of the war disguised as "Stanko Andras", a Slovakian laborer.

After 1945 he changed his surname from Hoffmann to Kishont to disguise his Jewish heritage and returned to Hungary to study art and publish humorous plays. He immigrated to Israel in 1949 to escape the Communist regime, and an immigration officer gave him the name Ephraim Kishon.

His first marriage, in 1946 to Eva (Chawa) Klamer, ended in divorce. In 1959, he married his second wife Sara (née Lipovitz), who died in 2002. In 2003, he married the Austrian writer Lisa Witasek. He had three children: Raphael (b. 1957), Amir (b. 1963), and Renana (b. 1968).

Acquiring a mastery of Hebrew with remarkable speed, Kishon started a regular satirical column in the easy-Hebrew daily, Omer, after 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.

Collections of his humorous writings have appeared in Hebrew and in translation. Among the English translations are 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).

His works have been translated into 37 languages, the majority of which were sold in Germany. Kishon rejected the idea of universal guilt for the Holocaust and had many friends in Germany. Kishon said “It gives me great satisfaction to see the grandchildren of my executioners queuing up to buy my books.” Friedrich Torberg was his congenial translator to German, until he died in 1979; thereafter Kishon himself wrote in German. Ultimately, he wrote over 50 books.

Kishon was a life-long chess enthusiast, and took an early interest in chess-playing computers.In 1990, German chess computer manufacturer Hegener & Glaser together with Fidelity produced the Kishon Chesster, a chess computer distinguished by the spoken comments it would make during a game. Kishon wrote the comments to be humorous, but were also carefully chosen to be relevant to chess and the position in the game.

In 1981, Kishon established a second home in the rural Swiss canton of Appenzell. He had come to feel somewhat estranged and unappreciated in Israel, believing that some native-born Israelis were against him because he was a Hungarian immigrant and that the literary establishment looked down on his best-selling "middle-brow" works. Kishon became increasingly conservative and continued to strongly support Zionism.

Among the numerous awards won by Kishon over the years are the following:

• In 1953, Kishon won the Israeli Nordau Prize for Literature;
• In 1958, he received the Israeli Sokolov Prize for Journalism;
• in 1964, he received the Israeli Kinor David Prize;
• In 1998, he was the co-recipient (jointly with Nurit Guvrin and Aryeh Sivan) of the Bialik Prize for literature;
• In 2002, he was awarded the Israel Prize for his lifetime achievement & special contribution to society and the State of Israel. He commented "I've won the Israel Prize, even though I'm pro-Israel. It's almost like a state pardon. They usually give it to one of those liberals who love the Palestinians and hate the settlers."

He also won two Academy Award nominations for best foreign language film, and three Golden Globe Award nominations, and two Golden Globe Best Foreign Language Film Awards, for Blaumlich Canal (1969) and The Policeman (1971) //en.wikipedia.org/wiki/Golden_Globe_Award_for_Best_Foreign_Language_Film#1960s.

• His reputation precedes him (1953)
• Ha-Ketubbah (1953)
• Take the plug out (1968)
• Oh, oh, Juliet (1972)
• Salah Shabati the musical. (1988)

His sketches and plays have been performed, in translation, on the stages and television networks of several countries.

Kishon wrote, directed and produced five feature films (all of them comedic and/or satirical). Three movies were nominated for major international awards, one of which went on to win (see below):

• Sallah Shabati (1964, nominated for Oscar for best foreign language film)
• Ervinka (1967)
• Blaumilch Canal, also known as The Big Dig (1969, nominated for Golden Globe 1971)
• Ha-Shoter Azoulay (literally, Constable Azoulay), also known as The Policeman (1971, nominated for Oscar for best foreign language film, awarded 1972 Golden Globe for best foreign language film)
• The Fox in the Chicken Coop (1978)

Kishon died in Switzerland at age 80, apparently of a heart attack. His body was returned to Israel and buried in the artists' cemetery in Tel Aviv.