In 1878, Eulenburg succeeded his first cousin once removed Friedrich Albrecht zu Eulenburg as Minister of the Interior, serving under Bismarck. He implemented a series of repressive anti-socialist measures. From 1881 to 1892 he was the president of Hesse-Kassel (or Hesse-Cassel) in Kassel. He was Minister-President of Prussia from 1892 to 1894 and, until Paul Hirsch in 1918, was the last Minister-President (Prime Minister) to not also hold the office of Imperial Chancellor.
Eulenburg was a second cousin of Prince Philip of Eulenburg, a close friend of Wilhelm II, German Emperor, and an instrumental figure behind the scenes of German politics. On October 25, 1875 he married at Neustadt, West Prussia Elisabeth von Alvensleben (born September 22, 1834 in Brandenburg/Havel; died September 5, 1919 in Neustadt), by whom he had an only son, Botho (born February 15, 1879 in Berlin; died May 30, 1881 in Berlin).
Appointed to the Prussian minister-presidency upon the recommendation of his predecessor, Count Caprivi, Eulenburg was an experienced administrator, having previously been governor of the Prussian province of Hesse. An avowed reactionary, he soon made life difficult for Caprivi, and often thought of pressing for his removal.
Eulenburg was eventually dismissed by Wilhelm II following the renewal of anti-Socialist moves (and an anti-subversion bill) in 1894. Eulenburg often thought of himself as the only possible successor to Caprivi, and he was extremely unhappy to be dismissed at what he regarded as the moment of his destiny. He died in Berlin.