In the years just preceding Hitler's rise to power in Germany in 1933, Einstein spent less and less time in Berlin until he ultimately left the country for good, spending the final two decades of his life at the Institute for Advanced Study in Princeton. However, one of the major reasons that for Einstein's early absences from Germany was not political but health-related; Einstein was consistently falling sick. In February of 1928 he became seriously ill on a visit to Switzerland. To assist him with his correspondence, he hired as his personal secretary Helen Dukas, an intelligent and efficient woman from Swabia. Helen traveled with the Einsteins on lecture tours, moved with them to the United States in 1933, and cared for Einstein after the death of his second wife Elsa in 1936.

In the summer of 1929, Einstein bought a plot of land in the small village of Capruth, near Berlin, where he could retreat from his hectic and oppressive life in the university. In December 1930, he left Germany to assume the position of visiting professor at California Institute of Technology (Caltech) for three months. There, he became acquainted with astronomer Edwin Hubble and his telescope project in Pasadena. When Einstein returned to Germany in March 1931, he spent most of his time working in the country home in Capruth. However, the Einsteins traveled abroad again in May, this time at the invitation to lecture at Oxford. There, Einstein accepted a five-year position at Christ Church, though he was obligated to spend only a short time at the college each year. Nonetheless, for the next two and a half years, Einstein spent a great deal of time either in Pasadena or at Oxford, glad to avoid an increasingly anti-Semitic and politically tense Germany.

In 1932, Einstein met the American educationalist Abraham Flexner, who had recently acquired funding for the construction of an advanced international science research institute in Princeton, New Jersey. In 1933, Einstein agreed to join the institute that autumn, intending to divide his time equally between Berlin and Princeton. However, when Adolf Hitler came to power in Germany on January 30, 1933, Einstein knew that he would never want to return to Germany again. Hitler and his National Socialist party were not just anti-Semitic, but also fervently anti-intellectual. Thus, Einstein was one of their chief enemies. The Nazis froze his bank account and seized his home while Einstein was still in America. When he returned to Europe in March 1933, he wrote a letter of resignation from the Prussian Academy of Sciences, Germany's most exclusive and prestigious learned society. Einstein also renounced his German citizenship once again as a sign of his opposition to National Socialism.

Following the Nazi rise to power in Germany, Einstein began to rethink his rigid pacifist stance. Although he had always insisted that violence and military action were inexcusable under any circumstances, he now realized that the present world situation was so grave that war was the only recourse. Thus, in spite of all his outspoken advocacy of universal disarmament in the early 1930s, Einstein accepted a position with the U.S. Navy during World War II, evaluating and approving plans for new weapons. In 1939, under the strong influence of the Hungarian nuclear physicist Leo Szilard, Einstein wrote a letter to President Roosevelt encouraging him to accelerate the process of creating and testing nuclear weapons. He tried to alert the President to the danger that the Axis might develop the new technology first. However, while Einstein was willing to write this letter, he did not want to be involved in the actual development of the atomic bomb. Thus he was not intimately involved in the Manhattan Project, and was deeply distressed upon learning that atomic bombs had been dropped on Hiroshima and then Nagasaki. From the end of the war until his death in 1955, Einstein campaigned relentlessly for the abolition of nuclear weapons. He was especially active in the Emergency Committee of Atomic Scientists, an organization established to educate the general public about atomic weapons, in order to pressure governments to behave morally and responsibly. Thus, in the years following the war, Einstein readopted a strong pacifist stance, once again advocating nuclear disarmament and international cooperation.