Christopher William Bradshaw-Isherwood was born in Cheshire, England, on August 26, 1904, to Kathleen Machell-Smith and Frank Bradshaw-Isherwood. His brother, Richard, was born in 1911. Frank Isherwood was in the British military and was required to move his family several times, much to Kathleen's displeasure. She sent Christopher to St. Edmund's boarding school for a proper education in 1914. There he met W. H. Auden, who was to become a life-long friend and co-author of several books and plays. The death of Isherwood's father on May 8, 1915, during a battle in France deeply affected him, not only in his perspective of his father and how he would relate to his mother, but in his attitude towards the military and war itself.

Isherwood met Edward Upward, a life-long friend and influence, in 1919 at Repton, a prestigious public school, and later joined him at Corpus Christi College, Cambridge, in 1923. In 1925, Isherwood was asked to withdraw from the university and so he took a job in London as a part-time secretary to a string quartet and began to write novels. The influence of E. M. Forster encouraged Isherwood to write and publish his first novel, in May of 1928.

Throughout Isherwood's life, he knew and worked with many people who influenced him and whom he influenced. He was known by the Bloomsbury group, and Hogarth Press published three of his books, (1932), (1938), and (1939). John Lehmann, a poet and an editor for the press, became a life-long friend to Isherwood and they supported each other in their work and in their personal lives.

Isherwood traveled to Berlin in 1929 to escape the social and sexual inhibitions that he felt in England. He then decided to live there and worked on his second novel (1932), and what was to become one of his best known works, the These stories offer an insight into the pre-Hitler era of Germany and were later developed into the musical

Isherwood lived in Berlin from 1930 to 1933. Trying to avoid the restraints that Hitler was enforcing on Germany, Isherwood and Heinz, his lover, traveled around Europe looking for a place to settle until 1937 when Heinz was forced to return to Germany to serve in the army. This affected Isherwood deeply. Losing the freedoms he had felt in Germany, and knowing that England could not offer better social conditions than before his departure in 1929, he and W. H. Auden began traveling in the Orient in 1938. During their travels they wrote, (1939). They went to the United States before returning to England. In 1939, the conditions in Europe were looking more as though war was inevitable, and Isherwood did not want to be a part of this, so he and Auden returned to the United States and decided to become American citizens. In New York, Isherwood did not find the haven he had hoped for and moved to California at the invitation of Gerald Heard. From October 1941, until July 1942, Isherwood lived in Haverford, Pennsylvania, and taught English to German refugees through the Society of Friends, a Quaker organization. Isherwood received his immigration papers and was a conscientious objector to the war, however, the age was lowered and he never had to serve his new country.

Isherwood returned to California and worked intermittently in motion picture studios in Hollywood for over 30 years. Due to this involvement, Isherwood met and worked with a variety of writers and other people who worked in the Hollywood community such as Tennessee Williams, Aldous Huxley, Kenneth Anger, Truman Capote, and Charles Laughton.

Living in Los Angeles, Isherwood became involved with Swami Prabhavanda, a Hindu monk who was head of the Vedanta Society of Southern California. This had a major impact on his life, providing a spiritual foundation that supported his social beliefs as well as his sexual identity. Isherwood had determined during his years in Berlin that freedom was more than what the left-wing was preaching at that time, and that the homophobia that prevailed in this movement was one of the obvious indications that this freedom was to be limited to a select few. By the 1970s, Isherwood had began to publicly discuss how homophobia was one aspect of the hate that must be overcome to reach a level of peace in the world.

Don Bachardy and Isherwood met in 1953 and became lovers in 1954. They worked together on number of motion pictures, television scripts, and on dramatizations of Shaw's story (1969) and Isherwood and Bachardy remained lovers until Isherwood died in 1986.