Teller officially joined the Manhattan Project, initially working at the Metallurgical Laboratory at the University of Chicago. His focus shifted to the theoretical aspects of nuclear chain reactions.

Teller moved to the Los Alamos Laboratory in New Mexico, where the atomic bomb design and construction were centralized. He was assigned to the Theoretical Division under Hans Bethe.

While contributing to the atomic bomb project, Teller became increasingly focused on the possibility of creating a far more powerful thermonuclear weapon, the hydrogen bomb (also known as 'the Super'). This interest often diverted his attention and resources from the primary goal of the Manhattan Project.

Teller witnessed the first successful test of an atomic bomb (the Trinity Test). This experience further fueled his conviction about the importance of nuclear weapons and his pursuit of the hydrogen bomb.