Vittorini's death in 1966 greatly affected Calvino. He went through what he called an "intellectual depression", which the writer himself described as an important passage in his life: "...I ceased to be young. Perhaps it's a metabolic process, something that comes with age, I'd been young for a long time, perhaps too long, suddenly I felt that I had to begin my old age, yes, old age, perhaps with the hope of prolonging it by beginning it early."

In the fermenting atmosphere that evolved into 1968's cultural revolution (the French May), he moved with his family to Paris in 1967, setting up home in a villa in the Square de Châtillon. Nicknamed L'ironique amusé, he was invited by Raymond Queneau in 1968 to join the Oulipo (Ouvroir de littérature potentielle) group of experimental writers where he met Roland Barthes, and Georges Perec, all of whom influenced his later production.[48] That same year, he turned down the Viareggio Prize for Ti con zero (Time and the Hunter) on the grounds that it was an award given by "institutions emptied of meaning".[49] He accepted, however, both the Asti Prize and the Feltrinelli Prize for his writing in 1970 and 1972, respectively. In two autobiographical essays published in 1962 and 1970, Calvino described himself as "atheist" and his outlook as "non-religious".[50]

Calvino had more intense contacts with the academic world, with notable experiences at the Sorbonne (with Barthes) and the University of Urbino. His interests included classical studies: Honoré de Balzac, Ludovico Ariosto, Dante, Ignacio de Loyola, Cervantes, Shakespeare, Cyrano de Bergerac, and Giacomo Leopardi. Between 1972 and 1973 Calvino published two short stories, "The Name, the Nose" and the Oulipo-inspired "The Burning of the Abominable House" in the Italian edition of Playboy. He became a regular contributor to the Italian newspaper Corriere della Sera, spending his summer vacations in a house constructed in the pinewood of Roccamare, in Castiglione della Pescaia, Tuscany.

In 1975 Calvino was made Honorary Member of the American Academy. Awarded the Austrian State Prize for European Literature in 1976, he visited Mexico, Japan, and the United States where he gave a series of lectures in several American towns. After his mother died in 1978 at the age of 92, Calvino sold Villa Meridiana, the family home in San Remo. Two years later, he moved to Rome in Piazza Campo Marzio near the Pantheon and began editing the work of Tommaso Landolfi for Rizzoli. Awarded the French Légion d'honneur in 1981, he also accepted to be jury president of the 29th Venice Film Festival.

During the summer of 1985, Calvino prepared a series of texts on literature for the Charles Eliot Norton Lectures to be delivered at Harvard University in the fall. On 6 September, he was admitted to the ancient hospital of Santa Maria della Scala in Siena where he died during the night between 18 and 19 September of a cerebral hemorrhage.[51] His lecture notes were published posthumously in Italian in 1988 and in English as Six Memos for the Next Millennium in 1993.