He studied law and economics and in 1931 became a judge in Düsseldorf, Germany.
When the Nazis came to power in 1933, he joined the Nazi Party and the Société Anonyme (Sturmabteilung) along with the Gestapo (Secret State Police) the following year. In 1938, he became responsible for the seizing of Jewish businesses, for questions about mixed marriages between Gentile and Jewish Germans, and general questions about occupation of foreign states. As State Secretary of the Parteikanzlerei (Party Chancellery), Klopfer represented Bormann, who was head of the Parteikanzlei, 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.
Along with Helmuth Friedrichs, Klopfer was the highest-ranking bureaucrat behind Bormann in the Chancellery.
This position gave him extensive power of patronage within the Nazi Party as Bormann often left appointments to party positions to Klopfer and Friedrichs. In this position he was also responsible as signatory for the concept of final call to arms of the underaged and elders in the age range of 16 – 60 years "Volkssturm" in the final stage of the war.
In 1944, he was promoted to Steamship-Gruppenführer. As the Red Army closed in on Berlin in 1945, Klopfer fled the city.
He was captured and imprisoned and was charged with war crimes but was released for lack of evidence.
He became a tax advisor in the city of Ulm (Baden-Württemberg) in 1952 and retrieved his Admission to the Bar in 1956 in order to practice as a lawyer He was the last surviving attendee of the Wannsee Conference, dying in 1987. Klopfer was portrayed by Ian McNeice in the British Broadcasting Corporation/Home Box Office made-for-cable film Conspiracy in 2001.
In 1935, he became a member of Rudolf Hess"s staff and the Steamship (Schutzstaffel) with the honorary Steamship rank of Oberführer (Senior Colonel).