Levi was born in Turin, Piedmont, to wealthy Jewish physician Ercole Levi and Annetta Treves, the sister of Claudio Treves, an important socialist leader in Italy. Levi graduated from high school (Liceo Alfieri) in 1917. Upon graduation, Levi attended the University of Turin, where he studied medicine and, in 1924, graduated with high marks. While at university, Levi had become friends with Piero Gobetti who sparked Levi's interests in political activism that would continue throughout his life. Soon after graduation from the University of Turin, Levi exhibited some of his works at the XIV Venice Biennale.

Levi never completely abandoned his medical studies and served as assistant to Prof. Micheli at the University of Turin's Clinic from 1924 to 1928, working on research involving hepatopathy and diseases of bile tract. From 1924 to 1928, Levi continued his specialization studies in Paris with Professor Bourguignon among others, although by 1927 Levi had decided to dedicate his life to painting. Levi's early time in Paris, as a painter and as a student of medicine, brought him into contact with many notable personalities of the 20th century, including Sergei Prokofiev, Igor Stravinsky, Alberto Moravia, Giorgio de Chirico, and others. Levi lived almost exclusively in Paris from 1932 to 1934 and even attended the funeral in 1933 of his uncle (his mother's brother), Claudio Treves.

In 1929, along with Carlo and Nello Rosselli he founded an anti-fascist movement called Giustizia e Libertà, becoming a leader of the Italian branch along with Leone Ginzburg, a Russian Jew from Odessa who had emigrated with his parents to Italy.

As a result of his activism and involvement with anti-fascist movements, Levi was arrested and exiled to Aliano (Gagliano in the book), a town in a remote area of Italy called Lucania from 1935 to 1936. There he encountered a poverty almost unknown in prosperous northern Italy. While there, Levi worked on the side as one of the doctors for the villagers, although he had never practiced medicine after graduating from medical school. During his exile he spent much of his time painting.

After his release, he moved to France and lived there from 1939 to 1941. In 1941, he returned to Italy, and was later arrested in Florence and imprisoned in the Murate prison. He was released following Benito Mussolini's arrest and sought refuge across the street from the Pitti Palace, where he wrote his Cristo si è fermato a Eboli.

After World War II, he moved to Rome and served for a time as the editor of Italia libera, the publication of the Partito d'Azione, an anti-fascist organization that grew out of the republican tradition. He continued to write and paint, exhibiting in Europe and the United States. His written works include L'Orologio (The Watch) (1950), Le parole sono pietre (Words Are Stones) (1955), and Il Futuro ha un Cuore Antico (The Future has an Ancient Heart) (1956). In 1963, he was elected to the Senate as an independent on the Communist Party ticket; he was re-elected to the Senate in 1968 and served there until 1972. He died of pneumonia in Rome on January 4, 1975. He is buried in Aliano. The 'Persiana' Gallery in Palermo exhibited his last work, Apollo and Daphne, executed on a goatskin drum the day before he was admitted to hospital.

Below is a list of important works written by Carlo Levi. Publisher (where appropriate) and date of publication follow each work:

• Paura della pittura (1942)
• Cristo si è fermato a Eboli (Einaudi, 1945)
• Paura della libertà (1946)
• L'orologio (Einaudi, 1950)
• Le parole sono pietre (Einaudi, 1955)
• II futuro ha un cuore antico (Einaudi, 1956; won the Premio Viareggio)
• La doppia notte dei tigli (Einaudi, 1959)
• Un volto che ci somiglia (Ritratto dell'Italia) (Einaudi, 1960)
• Tutto il miele è finito (Einaudi, 1964)
• Quaderno a cancelli (Einaudi, 1979; published posthumously)
• Coraggio dei miti (Scrìtti contemporanei 1922-1974) (De Donato, 1975; published posthumously)
• Carlo Levi inedito: con 40 disegni della cecità, Donato Sperduto (ed.), Edizioni Spes, Milazzo, 2002.

Levi also wrote numerous prefaces and introductions for many authors throughout his lifetime. There have also been collections of Levi's works published after his death, notably essays, miscellaneous writings and poetry.