During the time that the Party was banned in the wake of Adolf Hitler's failed Beer Hall Putsch of November 1923, Lohse joined the Völkisch-Social Bloc, a Nazi front organization, and was elected under its banner to the city council of Altona.

During this time, he also led into the Nazi Party various nationally-oriented farming associations in northern Germany, such as the Rural People's Movement.

[4] In November 1932, Lohse was elected to the Reichstag for electoral constituency 13 (Schleswig-Holstein) and retained this seat until the fall of the Nazi regime in May 1945.

He reported to Reichsminister Alfred Rosenberg of the Reich Ministry for the Occupied Eastern Territories and was responsible for the implementation of Nazi Germanization policies, which were built on the foundations of the Generalplan Ost: the killing of almost all Jews, Romani people, and Communists and the oppression of the local population that was its necessary corollary.

[9] Nevertheless, as the leader of the civil administration, he implemented, through a series of special edicts and guiding principles, many of the preparatory acts that facilitated the subsequent police Aktionen (the Nazi euphemism for killing operations).

These measures, first put forth in his decree of 27 July 1941, included compiling lists of Jews, mandating that they must wear the yellow badge, confiscating their property and banning them from public transportation, school attendance or employment in the professions.

On 31 October 1941, Georg Leibbrandt, a high official in the Reich Ministry, wrote to Lohse requesting an explanation for his order forbidding the execution of Jews in Liepāja.

Leibbrandt's deputy, Otto Bräutigam, responded on 18 December, informing Lohse that "Economic considerations should fundamentally remain unconsidered in the settlement of the [Jewish] problem".

Lohse fled the Reichskommissariat Ostland without authorization on 13 August 1944 in the face of the Red Army advance, and he was immediately removed as Reichskommissar.

Lohse returned to Gau Schleswig-Holstein where he continued to exercise absolute power as Gauleiter and Reich Defense Commissioner until the last days of the war in Europe.

In July of the same year, a finding by the Kiel denazification committee placed him in Group III (lesser offenders) and authorized him to receive a pension of 25% of an Oberpräsident's salary.

[14] However, in March 1952, the pension was revoked by the German government in Bonn under pressure from the Landtag of Schleswig-Holstein in protest of his antidemocratic rule in the province.