The book chronicles Oppenheimer's rise to fame as "the father of the atomic bomb" and director of the Manhattan Project, as well as his tragic downfall due to his security hearing in the McCarthy era.

This pivots Oppenheimer as an important historical figure and a symbol for atomic bomb ethics and political discourse about nuclear power.

His early life, ambitions, ideas, political activities, marriage, relationships with other women and physicists, misgivings about the bomb, complexities, and shortcomings are also discussed in the book.

The book served as inspiration for Christopher Nolan's 2023 biographical film Oppenheimer, starring Cillian Murphy as the theoretical physicist.

Oppenheimer commented on his childhood, "My life as a child did not prepare me for the fact that the world is full of cruel and bitter things.

Versatile in many subjects, Oppenheimer formed his own cult of admirers, established an international reputation as a scientist, and developed an interest in the humanities and literature, including Hindu scriptures.

While a professor at Berkeley, Oppenheimer began an intense relationship with graduate student Jean Tatlock, which instilled a new interest in social and political activism.

Amidst the Great Depression, Oppenheimer developed an appeal for the unemployed and migrant farmers and later gave donations for Spanish relief through the Communist Party of America (CPUSA) and funded refugees from Nazi Germany.

At Los Alamos, Oppenheimer became the scientific director of the Manhattan Project and transformed into a charismatic, effective, organized administrator and patriotic leader.

The book highlights how tight security, excess secrecy, and constant military surveillance burdened Oppenheimer and other scientists.

Bird and Sherwin argue that Oppenheimer was committed to his trustworthiness as a scientist and the project's success rather than to an invariable loyalty to the United States.

Oppenheimer was aware of possible targets in Japan and would play a vital part in the efficiency of the atomic bombings of Hiroshima and Nagasaki.

As chairman of the General Advisory Committee (GAC) of the Atomic Energy Commission, Oppenheimer opposed the accelerated construction of the Super (H-bomb).

In another meeting, Oppenheimer criticized communism and claimed he was "a resolute anti-communist" but continued to face suspicions and accusations of communist ties.

[6] The book shows how Oppenheimer, amidst a stalemate of Cold War policy, became more estranged from politics in Washington, while still fatefully trying to remain an insider.

Eventually, President Eisenhower attempted to cut off Oppenheimer from all government contacts and create a "blank wall" between the scientist and classified material.

The hearing board concluded that Oppenheimer was a security threat due to his past conduct and associations, stance on the hydrogen bomb, and less than candid responses.

According to Bird and Sherwin, the hearing was a crucial turning point in the relations between scientists and the government and proved a defeat for American liberalism.

Historian Martin J. Sherwin, who had previously written A World Destroyed: Hiroshima and Its Legacies (1975), started to work on the Oppenheimer biography in 1979,[10] and signed the first contract with the publisher, Knopf, on March 13, 1980, for $70,000.

[11] Thomas Powers writes that "historians of the subject, a small gossiping group, suggested that Sherwin was the latest victim of the curse of Oppenheimer".

[13] In 1999 Sherwin invited his friend, writer and editor Kai Bird,[11] who had already written two political biographies,[10] to join him and put it together in a cohesive and readable format.

[11] First comparison of the physicists who made the bomb possible to Prometheus was in the Scientific Monthly in September 1945: "Modern Prometheans have raided Mount Olympus again and have brought back for man the very thunderbolts of Zeus.

"[11] Janet Maslin wrote in her New York Times review that "American Prometheus aligns its subject's most critical decisions with both his early education and his ultimate unraveling.

Nolan continued a newfound interest in Oppenheimer, reading American Prometheus, and decided to base his screenplay on the book, centering on the security clearance hearings.

[11] According to Nolan, "he envisioned Oppenheimer not as a biography ('a formula that you write into can be creatively stifling') but more like "a thriller, a heist film, a courtroom drama".