Serber's lectures explaining the basic principles and goals of the project were printed and supplied to all incoming scientific staff, and became known as The Los Alamos Primer.

When the Los Alamos National Laboratory was first organized, Oppenheimer decided not to compartmentalize the technical information among different departments.

After receiving an identification card noting that his civilian noncombatant duties were commensurate in profile to the Army of the United States rank of colonel (an administrative designation only ostensibly valid if he were captured as a prisoner of war under the 1929 Geneva Convention, although he was frequently afforded salutations and other perquisites of the rank in practice by military personnel while traveling),[6] Serber was to go on Big Stink, the camera plane for the Nagasaki mission, as a technical advisor; however, it left without him when group operations officer Major James I. Hopkins ordered him off the plane because he had forgotten his parachute, reportedly after the B-29 had already taxied onto the runway.

[7] In 1948, Serber had to defend himself against anonymous accusations of disloyalty, mostly because his wife Charlotte's family were Jewish intellectuals with socialist leanings, and also because he tried to remove politics from discussions of the feasibility of the fusion bomb, leading to arguments with Edward Teller.

[10] Although he had been cleared of any potential wrongdoing at a subsequent hearing that year, he was denied a prerequisite security clearance for a Japanese physics conference in 1952, precipitating his refusal to join a Teller-chaired Department of Defense advisory group.

[11] While he reluctantly signed the loyalty oath stipulated by the Levering Act for Berkeley personnel in 1950, growing antagonism between Oppenheimer and the more conservative Lawrence eventually spurred his departure.

He also collaborated with Abraham Pais on meson studies and developed the Serber-Dancoff method, a refined technique for analyzing strong coupling.

Although largely bereft of any ideology, he refused to join the Defense Department-affiliated JASON consulting group because of his previous clearance issues and opposition to the Vietnam War.

After being diagnosed with Parkinson's disease, Charlotte Serber suffered from depression and took her own life with an overdose of sleeping pills on May 22, 1967.

In 1972, they purchased a 52-foot (16 m) ketch, with the intention of sailing through the Panama Canal and to Japan via the Galapagos Islands and Tahiti during Serber's sabbatical.