On 1 November 1933, he was named as a state prosecutor in Düsseldorf and, on 1 December, he became a Referent (consultant) in the Prussian Ministry of Agriculture, Land and Forests under Walther Darré.

As an Oberregierungsrat (Senior Government Councilor), he initially headed the Party component overseeing the Reich Interior Ministry.

By April 1941, he had advanced to the rank of Ministerialdirektor and headed Department III that oversaw coordination between the Party and all state components.

He became a close confidant of Martin Bormann who, on 12 May 1941, became head of the Party Chancellery, the successor organization to Hess' office.

[4] Klopfer represented Bormann at the Wannsee Conference on 20 January 1942, in which the details of the Final Solution of the Jewish Question were formalised, policies that culminated in the Holocaust.

[8] After his release, Klopfer underwent a denazification process by a German tribunal in March 1949 and was classified as a "minor offender" (category III), receiving a 2000 Reichsmark fine and three years probation.

Another investigation into Klopfer's participation in the Wannsee Conference that was initiated by the Ulm public prosecutor's office in September 1960 was closed on 29 January 1962 on the basis that "there was no way the accused could have prevented or obstructed the implementation of the mass murder program".