A month after assuming control, Groves finalized plans for a laboratory in Los Alamos, New Mexico. This facility was to be the epicenter of the Manhattan Project's research and development, and he wanted Oppenheimer to oversee it. The Los Alamos site became operational in March 1943. Oppenheimer knew that, for the project to proceed as quickly as necessary, he would need as many top scientists as possible working at Los Alamos. In the late 1920s while serving a joint appointment at UC Berkley and Caltech, Oppenheimer had become close friends with Linus Pauling. Remembering the success of their work together, Oppenheimer invited Pauling to join him as head of studies in chemistry at Los Alamos. Pauling, though intrigued by the scope of work being conducted there, was not interested. The nephritis was still affecting him and he didn't want to uproot his family from their comfortable home in Pasadena and move them to a military base in the middle of the New Mexico desert. Oppenheimer was persistent, though, and offered Pauling access to several liters of tritium, a radioactive isotope of hydrogen. Despite the lure of a rare and virtually unexplored molecule, Pauling cited his obligations to Caltech and the OSRD and put an end to Oppenheimer's recruitment pitch.

With Fermi producing more successes at the University of Chicago and the Los Alamos workers turning out data at an amazing rate, the bomb was nearly ready for testing by the spring of 1945. With the war in Europe over, the U.S. was hoping for a quick victory over Japan with unconditional surrender as the ultimate goal. Kokura, Niigata, Kyoto, and Hiroshima were named as the primary targets for a nuclear strike.

Leó Szilárd, who was directly responsible for the genesis of the bomb, was becoming concerned. He had always imagined the bomb as a threat rather than a weapon to be used against humans. In May 1945 Szilárd wrote a letter to Harry S. Truman, who had assumed the presidency following Roosevelt's death, warning him of the catastrophic effects of nuclear weapons. He suggested that a test be held within view of a Japanese audience so that the Japanese would be able to offer an informed surrender before suffering extensive loss of human life. When that argument failed, Szilárd launched a petition to prevent the dropping of atomic weapons over Japan.

On July 16, 1945 the first detonation of a nuclear weapon took place at Alamogordo, New Mexico in an event now known as the Trinity Test. The bomb was ready. On July 28, 1945, Japan rejected surrender under the terms of the Potsdam Declaration. Just over a week later, Little Boy was dropped on Hiroshima, Japan, killing approximately 100,000 people upon detonation. Three days later, Fat Man was released over Nagasaki, killing another 39,000 individuals.

The world was stunned. The Bomb had changed everything.