The novel first took shape in July 1946, when Clarke wrote "Guardian Angel", a short story that would eventually become Part I of Childhood's End. Clarke's portrayal of the Overlords as devils was influenced by John W. Campbell's depiction of the devilish Teff-Hellani species in The Mightiest Machine, first serialized in Astounding Stories in 1934. After finishing "Guardian Angel", Clarke enrolled at King's College London and served as the chairman of the British Interplanetary Society from 1946 to 1947, and later from 1951 to 1953. He earned a first-class degree in mathematics and physics from King's in 1948, after which he worked as an assistant editor for Science Abstracts. "Guardian Angel" was submitted for publication but was rejected by several editors, including Campbell. At the request of Clarke's agent and unbeknown to Clarke, the story was edited by James Blish, who rewrote the ending. Blish's version of the story was accepted for publication in April 1950 by Famous Fantastic Mysteries magazine. Clarke's original version of "Guardian Angel" was later published in the Winter 1950 issue of New Worlds magazine. The latter version published in New Worlds more closely resembles Part I of the novel, "Earth and the Overlords".
After Clarke's nonfiction science book The Exploration of Space (1951) was successfully received, he began to focus on his writing career. In February 1952, Clarke started working on the novelization of "Guardian Angel"; he completed a first draft of the novel Childhood's End in December, and a final revision in January 1953. Clarke travelled to New York in April 1953 with the novel and several of his other works. Literary agent Bernard Shir-Cliff convinced Ballantine Books to buy everything Clarke had, including Childhood's End, "Encounter in the Dawn" (1953), (which Ballantine retitled Expedition to Earth), and Prelude to Space (1951). However, Clarke had composed two different endings for the novel, and the last chapter of Childhood's End was still not finished. Clarke proceeded to Tampa Bay, Florida, to go scuba diving with George Grisinger, and on his way there visited his friend Frederick C. Durant - President of the International Astronautical Federation from 1953 to 1956 - and his family in the Washington Metropolitan Area, whilst he continued working on the last chapter. He then travelled to Atlanta, Georgia, where he visited Ian Macauley, a friend who was active in the anti-segregation movement. Clarke finished the final chapter in Atlanta while Clarke and Macauley discussed racial issues; these conversations may have influenced the development of the last chapter, particularly Clarke's choice to make the character of Jan Rodricks – the last surviving member of the human species – a black man.
Clarke arrived in Florida at the end of April. The short story, "The Man Who Ploughed the Sea", included in the Tales from the White Hart (1957) collection, was influenced by his time in Florida. While in Key Largo in late May, Clarke met Marilyn Mayfield, and after a romance lasting less than three weeks, they travelled to Manhattan and married at New York City Hall. The couple spent their honeymoon in the Pocono Mountains in Pennsylvania, where Clarke proofread Childhood's End. In July, Clarke returned to England with Mayfield, but it quickly became clear that the marriage would not last as Clarke spent most of his time reading and writing, and talking about his work. Further, Clarke wanted to be a father, and Marilyn, who had a son from a previous marriage, informed Clarke after their marriage that she could no longer have children. When Childhood's End was published the following month, it appeared with a dedication: "To Marilyn, For letting me read the proofs on our honeymoon." The couple separated after a few months together, but remained married for the next decade.
Ballantine wanted to publish Childhood's End before Expedition to Earth and Prelude to Space, but Clarke wanted to wait. He felt that it was a difficult book to release. He had written two different endings for the novel and was unsure of which to use. According to biographer Neil McAleer, Clarke's uncertainty may have been because of its thematic focus on the paranormal and transcendence with the alien Overmind. While the theme was used effectively by Clarke in the novel, McAleer wrote that "it was not science fiction based on science, which he came to advocate and represent". When he wrote Childhood's End, Clarke was interested in the paranormal, and did not become a sceptic until much later in his life. Ballantine convinced Clarke to let them publish Childhood's End first, and it was published on August 24, 1953, with a cover designed by American science fiction illustrator Richard M. Powers. Childhood's End first appeared in paperback and hardcover editions, with the paperback as the primary edition, an unusual approach for the 1950s. For the first time in his career, Clarke became known as a novelist.
Decades later, Clarke was preparing a new edition of Childhood's End after the story had become dated. After the book was first published, the Apollo missions landed humans on the Moon in 1969, and in 1989 US President George H. W. Bush announced the Space Exploration Initiative (SEI), calling for astronauts to eventually explore Mars. In 1990, Clarke added a new foreword and revised the first chapter, changing the venue for the space race from the Moon to Mars. Editions since have appeared with the original opening or have included both versions. "Guardian Angel" has also appeared in two short story collections: The Sentinel (1983), and The Collected Stories of Arthur C. Clarke (2001).