From 1908 to 1911, Mirbach served as the embassy clerk in Saint Petersburg, and then as political councillor for the German military command in Bucharest.

In 1915 he became the German ambassador in Greece, before being expelled from Athens in December 1916 when the Entente-leaning government of Eleftherios Venizelos took power.

Mirbach was assassinated at the German embassy in Moscow by Yakov Grigorevich Blumkin and Nikolai Andreyev at the request of the Central Committee of the Left Socialist-Revolutionaries, who were trying to reignite the war between Russia and Germany.

Blumkin entered Mirbach's residence in Moscow using forged papers and shot his victim at point blank range.

Coincidentally, a later relative, Andreas von Mirbach, would be murdered by the Red Army Faction at the West German Embassy siege in Stockholm in 1975.