Upon his return to the laboratory, he developed and applied coincidence circuits to the study of nuclear reactions, such as the Compton effect, cosmic rays, and the wave–particle duality of radiation, for which he would receive a share of the Nobel Prize in Physics in 1954.

Furthermore, he became a principal in the German nuclear energy project, also known as the Uranverein (Uranium Club), which was started in 1939 under the supervision of the Army Ordnance Office.

While there, he learned the Russian language and worked on theoretical physics problems related to his doctoral studies.

[5] On his return from Russia, Bothe continued his employment at the PTR under Hans Geiger in the Laboratory for Radioactivity there.

[6][7][8][9] In 1925, while still at the PTR, Bothe became a Privatdozent at the University of Berlin, which means that he had completed his Habilitation, and, in 1929, he became an ausserordentlicher Professor there.

[3][4] In 1927, Bothe began the study of the transmutation of light elements through bombardment with alpha particles.

That year, Bothe and his collaborator Herbert Becker bombarded beryllium, boron, and lithium with alpha particles from polonium and observed a new form of penetrating radiation.

Ludolf von Krehl, Director of the KWImF, and Max Planck, President of the Kaiser-Wilhelm Gesellschaft (KWG, Kaiser Wilhelm Society, today the Max Planck Society), had offered the directorship to Bothe to ward off the possibility of his emigration.

– who had done his doctorate with the Nobel Laureate James Franck and was highly recommended by Robert Pohl and Georg Joos, and Arnold Flammersfeld (1939–1941).

In these times, Gentner continued his research on the nuclear photoeffect, with the aid of the Van de Graaff generator, which had been upgraded to produce energies just under 1 MeV.

As a result of the visit, Gentner formed a cooperative relationship with Emilio G. Segrè and Donald Cooksey.

[19] After the armistice between France and Germany in the summer of 1940, Bothe and Gentner received orders to inspect the cyclotron Frédéric Joliot-Curie had built in Paris.

While in Paris, Gentner was able to free both Frédéric Joliot-Curie and Paul Langevin, who had been arrested and detained.

The invitees included Walther Bothe, Siegfried Flügge, Hans Geiger, Otto Hahn, Paul Harteck, Gerhard Hoffmann, Josef Mattauch, and Georg Stetter.

A second meeting was held soon thereafter and included Klaus Clusius, Robert Döpel, Werner Heisenberg, and Carl Friedrich von Weizsäcker.

With Bothe being one of the principals, Wolfgang Gentner, Arnold Flammersfeld, Rudolf Fleischmann, Erwin Fünfer, and Peter Jensen were soon drawn into work for the Uranverein.

For the Uranverein, Bothe, and up to 6 members from his staff by 1942, worked on the experimental determination of atomic constants, the energy distribution of fission fragments, and nuclear cross sections.

However the experimental setup involved a sphere of Siemens electro-graphite submerged in water, no air being present.

"[22] In any event, there were so few staff or groups that they could not repeat experiments to check results,[23][24][25][26] although in fact a separate group at Gottingen, led by Wilhelm Hanle, determined the cause of Bothe's error: "Hanle's own measurements would show that carbon, properly prepared, would in fact work perfectly well as a moderator, but at a cost of production in industrial quantities ruled prohibitive by [German] Army Ordnance".

[27] By late 1941 it was apparent that the nuclear energy project would not make a decisive contribution to ending the war effort in the near term.

The nuclear energy project thereafter maintained its kriegswichtig (important for the war) designation and funding continued from the military.

[3] During 1956 and 1957, Bothe was a member of the Arbeitskreis Kernphysik (Nuclear Physics Working Group) of the Fachkommission II "Forschung und Nachwuchs" (Commission II "Research and Growth") of the Deutschen Atomkommission (DAtK, German Atomic Energy Commission).

Other members of the Nuclear Physics Working Group in both 1956 and 1957 were: Werner Heisenberg (chairman), Hans Kopfermann (vice-chairman), Fritz Bopp, Wolfgang Gentner, Otto Haxel, Willibald Jentschke, Heinz Maier-Leibnitz, Josef Mattauch, Wolfgang Riezler [de], Wilhelm Walcher, and Carl Friedrich von Weizsäcker.

The reports were confiscated under the Allied Operation Alsos and sent to the United States Atomic Energy Commission for evaluation.