Reinhard Heydrich joined the Nazi Party and the SS in 1931. In July 1932, Himmler entrusted him with the organization and leadership of the Security Service (SD). He became Head of the Bavarian Political Police in April 1933, and Head of the Secret State Police Office in Berlin in 1934.

In June 1936, he became Head of the Security Police, and in September 1939 of the Reich Security Main Office (Reichssicherheitshauptamt – RSHA).  From 1938, Heydrich was a key figure in the expulsion and extermination of the European Jews. Since the annexation of Austria, the Security Service had excelled in organizing forced emigration. Following the November Pogrom of 1938, Heydrich had 26,000 Jews in Germany arrested and imprisoned in concentration camps. When war broke out on September 1, 1939, Heydrich ordered the ghettoization of all Jews and the establishment of Councils of Elders in all Jewish communities in Poland. After the attack on the Soviet Union he initially ordered the “Special Units” (Einsatzgruppen) to execute Communist functionaries and Jews old enough to serve in the military. The “Special Units” soon got the order to begin their systematic mass murder of the entire Jewish population within the occupied territory of the Soviet Union.

After receiving on July 31, 1941, a memorandum, signed by Göring, which authorized him to carry out the “Final Solution of the Jewish Question,” Heydrich made plans for the extermination of 11 million European Jews. On 20 January 1942, Heydrich chaired the Wannsee Conference, where he declared "Under suitable direction, the Jews should be brought to the East in the course of the Final Solution, for use as labor. In large labor gangs, with the sexes separated, the Jews capable of work will be transported to those areas and set to road-building, in the course of which, without doubt, a large part of them ("ein großteil") will fall away through natural losses. The surviving remnant, surely those with the greatest powers of resistance, will be given special treatment, since, if freed, they would constitute the germinal cell for the re-creation of Jewry."

Heydrich called a follow-up conference on March 6, 1942, which further discussed the problems of "mixed blood" individuals and mixed marriage couples. At this meeting, Stuckart argued that only first degree mischlings (persons with two Jewish grandparents) should be sterilized by force, after which they should be allowed to remain in Germany and undergo a "natural extinction". He stated, ”I have always maintained that it is extraordinarily dangerous to send German blood to the opposing side. Our adversaries will put the desirable characteristics of this blood to good use. Once the half Jews are outside of Germany, their high intelligence and education level, combined with their German heredity, will render these individuals born leaders and terrible enemies."

OnMay 27, 1942, Czech resistance fighters in Prague made an assassination attempt on him which led to his death on June 4, 1942.