In September 1943, U.S. Army Corps of Engineers General Leslie Groves (Paul Newman) who oversaw construction of the Pentagon is assigned to head the ultra-secret Manhattan Project, to beat the Germans in building an atomic bomb.
Groves picks University of California, Berkeley physicist J. Robert Oppenheimer (Dwight Schultz) to head the team at the project. Oppenheimer was familiar with northern New Mexico from his boyhood days when his family owned a cabin in the area. For the new research facility, he selects a remote location on top of a mesa adjacent to a valley called Los Alamos Canyon, northwest of Santa Fe.
The different personalities of the military man Groves and the scientist Oppenheimer often clash in keeping the project on track. Oppenheimer in turn clashes with the other scientists, who debate whether their personal consciences should enter into the project or whether they should remain purely researchers without personal feelings.
Nurse Kathleen Robinson (Laura Dern) and the young physicist Michael Merriman (John Cusack) question what they are doing. Working with little protection from radiation during an experiment, Michael drops a radioactive component during an experiment dubbed Tickling the Dragon's Tail and retrieves it by hand in order to avoid disaster, but is exposed to a terminal dose of radiation. In the base hospital nurse Kathleen can only watch as he develops massive swelling and deformation before dying a miserable death days later.
While the technical problems are being solved, military investigations are undertaken in order to thwart foreign espionage, especially from 'communist sympathizers' who might be associated with socialist organizations. The snooping reveals that Oppenheimer has had a young mistress, Jean Tatlock (Natasha Richardson), and he is ordered by the military to stop seeing her. After he breaks off their relationship without being able to reveal the secret reasons why, she is unable to cope with the heartache and is later found dead.
As the project continues in multiple sites across America, technical problems and delays cause tensions and strife. To avoid a single-point-of-failureplan, two separate bomb designs are implemented: a large, heavy plutonium bomb imploded using shaped charges ("Fat Man"), and an alternate design for a thin, less heavy uranium bomb triggered in a shotgun design ("Little Boy"). The bomb development culminates in a live detonation in south-central New Mexico at the Trinity Site in the Alamogordo Desert (05:29:45 on July 16, 1945), where everyone watches in awe at the spectacle of the first mushroom cloud with roaring winds, miles away.
During Oppenheimer's victory parade through the base camp, Klaus Fuchs can be seen in the background watching Oppenheimer pass.
In the end, both Fat Man and Little Boy were successful.