On 15 March 1921, Armenian student Soghomon Tehlirian assassinated Talaat Pasha—former grand vizier of the Ottoman Empire and the main architect of the Armenian genocide—in Berlin. At his trial, Tehlirian argued, "I have killed a man, but I am not a murderer"; the jury acquitted him.

Tehlirian came from Erzindjan in the Ottoman Empire but moved to Serbia before the war. He served in the Armenian volunteer units of the Russian army and lost most of his family in the genocide. Deciding to take revenge, he assassinated Harutiun Mgrditichian, who helped the Ottoman secret police, in Constantinople. Tehlirian joined Operation Nemesis, a clandestine program carried out by the Dashnaktsutyun (the Armenian Revolutionary Federation); he was chosen for the mission to assassinate Talaat due to his previous success. Talaat had already been convicted and sentenced to death by an Ottoman court-martial, but was living in Berlin with the permission of the Government of Germany. Many prominent Germans attended Talaat's funeral; the German Foreign Office sent a wreath saying, "To a great statesman and a faithful friend."

Tehlirian's trial was held 2–3 June 1921, and the defense strategy was to put Talaat on trial for the Armenian genocide. Extensive evidence on the genocide was heard, resulting in "one of the most spectacular trials of the twentieth century", according to Stefan Ihrig. Tehlirian claimed he had acted alone and that the killing was not premeditated, telling a dramatic and realistic, but untrue, story of surviving the genocide and witnessing the deaths of his family members. The international media widely reported on the trial, which brought attention and recognition of the facts of the Armenian genocide; Tehlirian's acquittal brought mostly favorable reactions.

Both Talaat Pasha and Tehlirian are considered by their respective sides to be heroes; historian Alp Yenen refers to this relationship as the "Talat–Tehlirian complex". Talaat was buried in Germany, but Turkey repatriated his remains in 1943 and gave him a state funeral. Polish-Jewish lawyer Raphael Lemkin read about the trial in the news and was inspired to conceptualize the crime of genocide in international law.

As the leader of the Committee of Union and Progress (CUP), Talaat Pasha (1874–1921) was the last powerful grand vizier of the Ottoman Empire during World War I. Considered the primary architect of the Armenian genocide, he ordered the deportation of nearly all of the empire's Armenian population to the Syrian Desert in 1915, to wipe them out. Of 40,000 Armenians deported from Erzurum, it is estimated that fewer than 200 reached Deir ez-Zor. When more Armenians survived than Talaat had intended, he ordered a second wave of massacres in 1916. Talaat estimated that around 1,150,000 Armenians disappeared during the genocide. In 1918, Talaat told journalist Muhittin Birgen [tr], "I assume full responsibility for the severity applied" during the Armenian deportation and, "I absolutely don't regret my deed."

When United States ambassador Henry Morgenthau tried to persuade Talaat to discontinue the atrocities, he interrupted, saying he would not reconsider because most of the Armenians were already dead: "The hatred between the Turks and the Armenians is now so intense that we have got to finish with them. If we don't, they will plan their revenge." Talaat told Turkish writer Halide Edib that the extermination of Armenians was justified to advance Turkish national interests and that, "I am ready to die for what I have done, and I know that I shall die for it." In August 1915, after learning about the Armenian massacres, CUP former finance minister Cavid Bey predicted Talaat would be assassinated by an Armenian.

During World War I, Imperial Germany was a military ally of the Ottoman Empire. Ambassador Hans von Wangenheim approved limited removals of Armenian populations from sensitive areas. German representatives issued occasional diplomatic protests when the Ottomans went far beyond this in an attempt to contain the reputational damage from their allies' actions. Germany censored information about the genocide and undertook propaganda campaigns denying it and accusing Armenians of stabbing the Ottoman Empire in the back. Germany's inaction led to accusations that it was responsible for the genocide, which became entangled with the debate over Germany's responsibility for the war.

After the Armistice of Mudros (30 October 1918), following elaborate preparations, Talaat fled Constantinople on a German torpedo boat with other CUP leaders—Enver Pasha, Djemal Pasha, Bahaeddin Şakir, Nazım Bey, Osman Bedri, and Cemal Azmi—on the night of November 1-2. Except for Djemal, all were major perpetrators of the genocide; they left to evade punishment for their crimes and to organize a resistance movement. German foreign minister Wilhelm Solf had instructed the embassy in Constantinople to aid Talaat and refused the Ottoman government's request to extradite him, on the grounds that "Talaat has been loyal to us, and our country remains open to him."