Born in Tébessa in French Algeria, he moved to France in 1918. A professor of English Literature at several universities, during World War II Merle was consripted in the French army and assigned as an interpreter to the British Expeditionary Force. He ended up in Dunkerque where he was not evacuated but captured by the Germans. Merle used his experiences in his 1949 novel Week-end at Zuydcoote that won the Prix Goncourt. It was filmed in 1964.

He has also written a 13 book series of historical novels, Fortune de France. Recreating 16th and 17th century France through the eyes of a fictitious Protestant doctor turned spy, he went so far as to write it in the period's French making it virtually untranslatable.

His novels Un animal doué de la raison (A Sentient Animal, 1967), a stark Cold War satire inspired by John Lilly's studies of dolphins and the Caribbean Crisis, and Malevil (1972), a post-apocalyptic story, were both translated into English and filmed, the former, in 1973, as The Day of the Dolphin. It starred George C.Scott and had a screenplay by Buck Henry. It bore very little resemblance to Merle's story.

He died of a heart attack at his home La Malmaison in Grosrouvre near Paris.

• Week-end à Zuydcoote (1949) - Published in US as Week-end at Zuydcoote (1950)
• La mort est mon métier (1952) - Published in UK as Death is my Trade (1954)
• L'île (1962) - Published in US as The Island (1964)

• Moncada, premier combat de Fidel Castro (1965)
• Un animal doué de raison (1967) - Published in US as The Day of the Dolphin (1967)
• Derrière la vitre (1970) - Published in US as Behind the Glass (1972)
• Malevil (1972)
• Les hommes protégés (1974) - Published in US as The Virility Factor (1977)
• Madrapour (1976)
• L'idole (1987) - Published in US as The Idol
• Le Soleil ne se lève pas pour nous (1987)
• Le propre de l'homme (1989)

Fortune de France series (1977-2003)

1. Fortune de France (1977)
2. En nos vertes années (1979)
3. Paris ma bonne ville (1980)
4. Le prince que voilà (1982)
5. La violente amour (1983)
6. La Pique du jour (1985)
7. La volte des vertugadins (1991)
8. L’Enfant-Roi (1993)
9. Les Roses de la vie (1995)
10. Le Lys et la Pourpre (1997)
11. La Gloire et les Périls (1999)
12. Complots et Cabales (2001)
13. Le glaive et les amours (2003)