He is best known as the main leader of the Black Hand, a paramilitary secret society devoted to South Slav irredentism that organised the 1903 overthrow of the Serbian government and assassination of King Alexander I of Serbia and Queen Draga.

In 1916, the government in exile of Serbian Prime Minister Nikola Pašić, who considered Dimitrijević's refusal to compromise on South Slav irredentism to represent a serious threat to the secret peace negotiations taking place with Vienna during the Sixtus Affair, filed charges of high treason against the leadership of Unification or Death.

On 11 June 1903 the plotters succeeded when Dimitrijević and a group of junior officers stormed the royal palace and killed King Alexander, his wife, Queen Draga and three others.

In his memoirs, former Imperial Russian Foreign Office official Dmitri Abrikosov traced the inception of the Russo-Serbian military alliance that helped cause the First World War to the immediate aftermath of the 1903 palace coup and regicide.

In 1911 he helped founding Ujedinjenje ili Smrt (Unification or Death), commonly known as the Black Hand, a conspiratorial network supporting the formation of a Greater Serbia state.

[6] Dimitrijević's main objective was the liberation and unification of all Serb populated regions under Ottoman or Austro-Hungarian rule, this became more urgent after the monarchy annexed Bosnia and Herzegovina in 1908 provoking the Bosnian Crisis.

In early 1914 after finding out that three young Bosnian Serb students, led by nineteen year old Gavrilo Princip, were plotting to assassinate the heir to the Austro-Hungarian Empire, during his upcoming visit to Sarajevo,[9] the Black Hand provided the conspirators with weapons and training in Belgrade.

[11] However, his orders were not implemented, and the three men arrived in what was then known as the Condominium of Bosnia and Herzegovina, where they joined forces with fellow conspirators recruited by Princip's former roommate Danilo Ilić,[12] Veljko and Vaso Čubrilović, Muhamed Mehmedbašić, Cvjetko Popović and Miško Jovanović.

The failure of these cyanide capsules to work properly allowed the conspirators, who had received absolutely no training in how to withstand interrogation, to be easily tricked by Austrian police detectives and investigative magistrates into confessing and revealing the Colonel's involvement.

[20] In justifying the use of the death penalty, Prime Minister Pašić wrote to his envoy in London: "...Dimitrijević (Apis) besides everything else admitted he had ordered Franz Ferdinand to be killed.