Kesey wrote the book after working the night shift as an orderly at a mental hospital in California. He earned a degree in speech and communication from the University of Oregon and later studied creative writing at Stanford University, where he was taught by novelist Wallace Stegner, who went on to win a Pulitzer Prize in 1972.
While at Stanford, Kesey volunteered for a CIA project to study the effects of LSD and other psychedelic drugs being conducted at the Menlo Park Veterans Hospital. Kesey wrote extensively about the experiment and his experiences with the drugs and at the hospital. The experiences were the inspiration for Cuckoo's Nest.
Kesey's second published novel, Sometimes A Great Notion (1964), tells the story of an independent logging clan that helps break a strike at an Oregon sawmill. It is considered a masterpiece in Western American literature. The book was adapted as a 1971 film starring Paul Newman.
When Kesey had to travel to New York for the publication of his second book, his friend Beat writer Neal Cassady organized a cross-country trip in a psychedelic-painted school bus with a group of hangers-on called The Merry Pranksters. Tom Wolfe wrote about the trip in his book The Electric Kool-Aid Acid Test (1968). Kesey also wrote about the trip in his play The Further Inquiry, named after the bus' nickname,
Further. The Merry Pranksters also took the bus to Woodstock in 1969 without Kesey but it was worn out after that so Kesey parked it in a swamp on his Oregon farm in 1989 and bought a new bus, which was painted like the original and also called Further. In 2005, Kesey's son, Zane, pulled the original out of the swamp, and he and a group of original Pranksters have plans to restore it. Both buses remain parked a Kesey's farm.