Turkevich moved to the Department of Physics at the University of Chicago as a research assistant with Robert Mulliken where he studied molecular spectroscopy and nuclear fission products.
In 1942, during World War II, he joined the Manhattan Project, working initially at Columbia University. The Columbia laboratory group was asked to move to Chicago as part of the project and from 1943 to 1945 he worked at the Metallurgical Laboratory or "Met Lab", at the University of Chicago. He investigated the separation of uranium isotopes by gaseous diffusion of uranium hexafluoride and the radiochemistry of reactor products, such as plutonium, that are generated by neutron capture in uranium. In 1945, he transferred to Los Alamos, and was involved with the Trinity test, the first detonation of a nuclear device, near Alamogordo, New Mexico, on July 16, 1945. Turkevich was one of several scientists who estimated the amount of energy released in the explosion. He then transferred to Edward Teller's theory group to study nuclear fusion and establish whether producing a thermonuclear weapon was feasible, one of many challenges faced by scientists at Los Alamos that led to the development and use of the Monte Carlo method. He worked with Nicholas Metropolis and Stanley Frankel using the ENIAC computer.
Turkevich returned to the Department of Chemistry at the University of Chicago as an assistant professor in 1946. In July 1946, Turkevich and Seymour Katcoff suggested that nuclear explosions could be monitored by measuring the atmospheric concentration of the radioactive isotope krypton-85, a fission product. Turkevich wrote a letter to Philip Morrison proposing that atmospheric sampling could be used to estimate the number of fissions that had occurred in nuclear reactors and atmospheric atom bomb tests. The history of this aspect of Turkevichs work didnt become public until it was declassified in 1997.
He also worked on the peaceful uses of nuclear energy. For this latter work, he received the 1969 Atoms for Peace Award.