Though Heisenberg submitted to the Nazi regime when necessary, his cooperation was insufficient. He often avoided overt public acknowledgement of the Third Reich, using the separation of science and politics as his excuse. Moreover, he publicly opposed the efforts of Philipp Lenard and Johannes Stark to completely discredit Einstein's work. Lenard and Stark were Nobel Prize-winning experimental physicists whose areas of specialty had long since become irrelevant. Indeed, their declarations against Einstein's work as "Jewish physics"–they believed that science was fundamentally connected to the individual and his race and religion–were not a little influenced by their jealousy of Einstein's renown. Heisenberg could not allow such unreasoned criticism to pass unchallenged, and his opposition was seen as insubordination. Lenard and Stark focused much of their propaganda against Heisenberg, and as they were gaining administrative power, they also succeeded in blocking his appointment to Munich to succeed Sommerfeld.

In 1937 Heisenberg was married to Elisabeth Schumacher, thirteen years his junior. That he should choose a young woman was not a surprise, as he had complained recently that he needed youth to sustain him. A book dealer, Elisabeth had been invited to a party in Heisenberg's social circle, and they had met as he was playing the piano. She provided him with a sense of stability and acceptance at a time when he was feeling increasingly isolated, especially due to the worsening conditions of his country. The couple would have seven children and remain together for the rest of their lives.

Meanwhile, Heisenberg's fight for the Munich appointment continued. A petition signed by nearly all the physicists in Germany had apparently quelled the efforts of Lenard and Stark to defeat theory in general and Heisenberg in particular. However, Stark made one final attempt to prevent Heisenberg's formal appointment, publishing an article that appeared on the day of Heisenberg's arrival in Munich, two weeks before he was to assume his chair. The article essentially accused him of carrying the "Jewish spirit," which was considered worse than simply being Jewish. Heisenberg cleared his name only after months of struggle and an appeal to Heinrich Himmler, to whose family Heisenberg was connected through his mother. However, the mere approval of Himmler would not be enough, for Heisenberg also had to convince his enemies that he was loyal to the regime. At a time when he likely faced considerable personal danger, he saved himself only by making great compromises. As a teacher, for example, he could not mention the names of Jewish scientists, and as a citizen, he had to serve in the German military. If war had broken out in 1938, he would have been sent to the front lines. Despite his compromises, however, he still lost the Munic appointment.

Heisenberg's work, in the meantime, focused largely on nuclear decay, along the lines of the research Enrico Fermi had started. Heisenberg proposed the revolutionary "shower theory" to describe cosmic radiation as explosion-like. When Heisenberg brought this theory to the United States, his audience dwelled more on the question of why he had chosen to remain in Germany than on his work in shower theory. Perhaps implicitly, audiences recoiled from accepting his work because German physics was on the decline, while American research was on the rise.

War broke out in Europe on September 1, 1939. Heisenberg was fully prepared to serve his country, and he expected orders to report to the front. But the army had better use for its leading physicists: Heisenberg and several of his experimentalist colleagues were organized into a "uranium club" that would begin the investigation of nuclear fission and its potential applications to the war. From the beginning, Heisenberg did not believe that either side would accomplish its task in time to be useful for the war.

For his side, at least, Heisenberg proved to be correct. Perhaps in part due to a lack of resources, the Germans failed to achieve much success in the path toward nuclear weapons. In a famous meeting with Bohr in September 1941, Heisenberg may have hinted otherwise, and many have speculated on his intentions in going to Copenhagen. In all likelihood, he was not attempting some kind of warning or truce agreement, but Bohr left with the suspicion that Heisenberg was hinting at the extent of German progress. In any case, the relationship between the two would never be as close as it was before the war.

In 1942, Heisenberg was invited to Berlin to serve as the director of the Kaiser Wilhelm Institute for Physics and assume a chair in theoretical physics at the University of Berlin. Progress on the bomb was slow, and he devoted much of his time to other work.

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