Chamberlain was born on May 18, 1915, in Charlotte, North Carolina, as the son of Henry Bryan Chamberlain and the former Elizabeth Wolverton. When he was two years old the family moved to Ohio and he grew up in Lakewood, Ohio. From the time of junior high school on, he was interested in creative writing, working on poems, short stories, and an incomplete novel. While at Lakewood High School, which he began as the Great Depression was starting, he took third prize in national Scholastic Art & Writing Awards with a short story called "Hunger". Another short story, "A Millionaire's Debut", was published in the Cleveland News.
During vacations when he was 17 and 18, Chamberlain traveled around the country by hitchhiking and freighthopping. A San Francisco newspaper recounted his 7,000-mile (11,000 km) wandering journey with another 18-year-old friend from Cleveland to there, in which they started with only $3.77, washing dishes for funds while staying in hobo jungles and sometimes encountering long waits for cars to pick them up. By the age of 19, he said he had traveled some 23,000 miles (37,000 km) and seen 41 states. He offered to give 15-minute talks, titled "The Category of Dreamers" and concerning the state of youth, in the Lakewood area.
He attended Adelbert College of Western Reserve University, having been granted a scholarship, and initially majored in history. He was elected Phi Beta Kappa as a senior. He was also a poet there, winning first prize as a junior and second prize as a senior in the Rupert Hughes Prizes in Poetry. In 1937, he graduated with an A.B. degree magna cum laude.
Chamberlain was initially primarily interested in writing as a career possibility. While a freshman he was also working as editor of the People's Penny Weekly, a magazine intended to provide local coverage of Lakewood. During his senior year in college he worked part-time at the Cleveland bureau of the International News Service. There he covered many significant developments in labor relations during the mid-1930s. These included the Fisher Body sit-down strike against General Motors.
By his account he then tried two other writing and editing jobs before, after a year's lapse, returning to his education to give himself an understanding of the forces at play in these labor disputes. At the Graduate School at Western Reserve University, he earned an M.A. degree in economics in 1939. At the same time he wrote a play about the Chrysler Auto Strike of 1939, From Now to Hallelujah, which he later said was accepted for production at a local theater group but never put on due to a scheduling conflict. He also later recalled functioning as executive secretary of a successful campaign to amend the Cleveland city charter to bring most civil service employees under the merit system.