In the mid-19th century, the three major European powers, Great Britain, France and Russia, began to question the Ottoman Empire's treatment of its Christian minorities and pressure it to grant equal rights to all its subjects. From 1839 to the declaration of a constitution in 1876, the Ottoman government instituted the Tanzimat, a series of reforms designed to improve the status of minorities.

The Treaty of Berlin (formally the Treaty between Austria-Hungary, France, Germany, Great Britain and Ireland, Italy, Russia, and the Ottoman Empire for the Settlement of Affairs in the East) was signed on 13 July 1878. In the aftermath of the Russian victory against the Ottoman Empire in the Russo-Turkish War of 1877–1878, the major powers restructured the map of the Balkan region. They reversed some of the extreme gains claimed by Russia in the preliminary Treaty of San Stefano, but the Ottomans lost their major holdings in Europe. It was one of three major peace agreements in the period after the 1815 Congress of Vienna. It was the final act of the Congress of Berlin (13 June – 13 July 1878) and included Great Britain and Ireland, Austria-Hungary, France, Germany, Italy, Russia and the Ottoman Empire. Germany's Otto von Bismarck was the chairman and dominant personality.

In May 1895, the Powers forced Abdul Hamid II (Ottoman Empire Sultan) to sign a new reform package designed to curtail the powers of the Hamidiye, but, like the Berlin Treaty, it was never implemented.

On 1 October 1895, 2,000 Armenians assembled in Constantinople to petition for the implementation of the reforms, but Ottoman police units violently broke the rally up. Soon, massacres of Armenians broke out in Constantinople and then engulfed the rest of the Armenian-populated provinces of Bitlis, Diyarbekir, Erzurum, Harput, Sivas, Trabzon, and Van. Estimates differ on how many Armenians were killed, but European documentation of the pogroms, which became known as the Hamidian massacres, placed the figures at between 100,000 and 300,000.

In 1902, during a congress of the Young Turks held in Paris, the heads of the liberal wing, Sabahaddin and Ahmed Riza Bey, partially persuaded the nationalists to include in their objectives ensuring some rights for all the minorities of the empire.

On 24 July 1908, Armenians' hopes for equality in the Ottoman Empire brightened when a coup d'état staged by officers in the Ottoman Third Army based in Salonika removed Abdul Hamid II from power and restored the country to a constitutional monarchy. The officers were part of the Young Turk movement that wanted to reform administration of the perceived decadent state of the Ottoman Empire and modernize it to European standards.

A countercoup took place in early 1909, ultimately resulting in the 31 March Incident on 13 April 1909. Some reactionary Ottoman military elements, joined by Islamic theological students, aimed to return control of the country to the Sultan and the rule of Islamic law. Riots and fighting broke out between the reactionary forces and CUP forces, until the CUP was able to put down the uprising and court-martial the opposition leaders.

In 1912, the First Balkan War broke out and ended with the defeat of the Ottoman Empire as well as the loss of 85% of its European territory. Many in the empire saw their defeat as "Allah's divine punishment for a society that did not know how to pull itself together". The Turkish nationalist movement in the country gradually came to view Anatolia as their last refuge. The Armenian population formed a significant minority in this region.

By 1914, Ottoman authorities had already begun a propaganda drive to present Armenians living in the Ottoman Empire as a threat to the empire's security.

Occurred in June 1914, as part of the ethnic cleansing policies of the Ottoman Empire. It was perpetrated by irregular Turkish bands against the predominantly ethnic Greek town of Phocaea, modern Foça, on the east coast of the Aegean Sea. The massacre was part of a wider anti-Greek campaign of genocide launched by the Young Turk Ottoman authorities, which included boycott, intimidation, forced deportations, and massive killings; and was one of the worst attacks during the summer of 1914.

In November 1914 Shaykh ul-Islam proclaimed Jihad (Holy War) against the Christians: this was later used as a factor to provoke radical masses in the implementation of the Armenian Genocide.

On 2 November 1914, the Ottoman Empire opened the Middle Eastern theater of World War I by entering hostilities on the side of the Central Powers and against the Allies. The battles of the Caucasus Campaign, the Persian Campaign, and the Gallipoli Campaign affected several populous Armenian centers. Before entering the war, the Ottoman government had sent representatives to the Armenian congress at Erzurum to persuade Ottoman Armenians to facilitate its conquest of Transcaucasia by inciting an insurrection of Russian Armenians against the Russian army in the event a Caucasus front was opened.

On 24 December 1914, Minister of War Enver Pasha implemented a plan to encircle and destroy the Russian Caucasus Army at Sarikamish in order to regain territories lost to Russia after the Russo-Turkish War of 1877–1878. Enver Pasha's forces were routed in the battle, and almost completely destroyed. Returning to Constantinople, Enver Pasha publicly blamed his defeat on Armenians in the region having actively sided with the Russians.

The Russian Empire's response to the bombardment of its Black Sea naval ports was primarily a land campaign through the Caucasus. Early victories against the Ottoman Empire from the winter of 1914 to the spring of 1915 saw significant gains of territory, including relieving the Armenian bastion resisting in the city of Van in May 1915. The Russians also reported encountering the bodies of unarmed civilian Armenians as they advanced.

On 25 February 1915, the Ottoman General Staff released the War Minister Enver Pasha's Directive 8682 on "Increased security and precautions" to all military units calling for the removal of all ethnic Armenians serving in the Ottoman forces from their posts and for their demobilization. They were assigned to the unarmed Labor battalions. The directive accused the Armenian Patriarchate of releasing State secrets to the Russians. Enver Pasha explained this decision as "out of fear that they would collaborate with the Russians".

On 19 April 1915, Jevdet Bey demanded that the city of Van immediately furnish him 4,000 soldiers under the pretext of conscription. However, it was clear to the Armenian population that his goal was to massacre the able-bodied men of Van so that there would be no defenders. Jevdet Bey had already used his official writ in nearby villages, ostensibly to search for arms, but in fact to initiate wholesale massacres. The Armenians offered five hundred soldiers and exemption money for the rest in order to buy time, but Jevdet Bey accused the Armenians of "rebellion" and asserted his determination to "crush" it at any cost. "If the rebels fire a single shot", he declared, "I shall kill every Christian man, woman, and" (pointing to his knee) "every child, up to here".

On the night of 23–24 April 1915, known as Red Sunday, the Ottoman government rounded up and imprisoned an estimated 250 Armenian intellectuals and community leaders of the Ottoman capital, Constantinople, and later those in other centers, who were moved to two holding centers near Angora (Ankara).

In May 1915, Mehmet Talaat Pasha requested that the cabinet and Grand Vizier Said Halim Pasha legalize a measure for the deportation of Armenians to other places due to what Talaat Pasha called "the Armenian riots and massacres, which had arisen in a number of places in the country". However, Talaat Pasha was referring specifically to events in Van and extending the implementation to the regions in which alleged "riots and massacres" would affect the security of the war zone of the Caucasus Campaign. Later, the scope of the deportation was widened in order to include the Armenians in the other provinces.

On 24 May 1915, the Triple Entente (Russian Empire, France & UK) warned the Ottoman Empire that "In view of these new crimes of Turkey against humanity and civilization, the Allied Governments announce publicly to the Sublime Porte that they will hold personally responsible for these crimes all members of the Ottoman Government, as well as those of their agents who are implicated in such massacres".

On 29 May 1915, the Committee of Union and Progress (CUP) Central Committee passed the Temporary Law of Deportation ("Tehcir Law"), giving the Ottoman government and military authorization to deport anyone it "sensed" as a threat to national security.

Many Americans spoke out against the genocide, including former president Theodore Roosevelt, Rabbi Stephen Wise, Alice Stone Blackwell, and William Jennings Bryan, the U.S. Secretary of State to June 1915.

Although a neutral state throughout the war, Sweden had permanent representatives in the Ottoman Empire who closely followed and continuously reported on major developments there. Its embassy in Constantinople was led by Ambassador Cossva Anckarsvärd, with M. Ahlgren as envoy and Captain Einar af Wirsén as military attaché. On 7 July 1915, Ambassador Anckarsvärd dispatched a two-page report concerning the Armenian massacres to Stockholm.

As the orders for deportations and massacres were enacted, many consular officials reported what they were witnessing to Ambassador Henry Morgenthau, Sr., who described the massacres as a "campaign of race extermination" in a telegram sent to the United States Department of State on 16 July 1915. In memoirs that he completed during 1918.

By August 1915, The New York Times repeated an unattributed report that "the roads and the Euphrates are strewn with corpses of exiles, and those who survive are doomed to certain death. It is a plan to exterminate the whole Armenian people".

On 9 August 1915, Anckarsvärd (Ambassador of Sweden) dispatched yet another report, confirming his suspicions regarding the plans of the Turkish government, "It is obvious that the Turks are taking the opportunity to, now during the war, annihilate the Armenian nation so that when the peace comes no Armenian question longer exists".

The Tehcir Law brought some measures regarding the property of the deportees, and on 13 September 1915, the Ottoman parliament passed the "Temporary Law of Expropriation and Confiscation," stating that all property, including land, livestock, and homes belonging to Armenians, was to be confiscated by the authorities.

Typhoid inoculation: The Ottoman surgeon, Dr. Haydar Cemal wrote "on the order of the Chief Sanitation Office of the Third Army in January 1916, when the spread of typhus was an acute problem, innocent Armenians slated for deportation at Erzincan were inoculated with the blood of typhoid fever patients without rendering that blood 'inactive'".

On the night of 2–3 November 1918 and with the aid of Ahmed Izzet Pasha, the Three Pashas (which include Mehmet Talaat Pasha and Ismail Enver Pasha, the main perpetrators of the Genocide) fled the Ottoman Empire.

Lt. Hasan Maruf of the Ottoman army describes how a population of a village were taken all together and then burned. The Commander of the Third Army Vehib's 12-page affidavit, which was dated 5 December 1918, was presented in the Trebizond (Trabzon) trial series (29 March 1919) included in the Key Indictment, reporting such a mass burning of the population of an entire village near Muş: "The shortest method for disposing of the women and children concentrated in the various camps was to burn them".

Trabzon was the main city in Trabzon province; Oscar S. Heizer, the American consul at Trabzon, reported: "This plan did not suit Nail Bey ... Many of the children were loaded into boats and taken out to sea and thrown overboard". Hafiz Mehmet, a Turkish deputy serving Trabzon, testified during a 21 December 1918 parliamentary session of the Chamber of Deputies that "the district's governor loaded the Armenians into barges and had them thrown overboard".

In 1919, after the Mudros Armistice, Sultan Mehmed VI was ordered to organize courts-martial by the Allied administration in charge of Constantinople to try members of the Committee of Union and Progress (CUP) for taking the Ottoman Empire into World War I.

During the Paris Peace Conference, the Armenian delegation presented an assessment of $3.7 billion (about $53 billion today) worth of material losses owned solely by the Armenian church.

Morphine overdose: During the Trabzon trial series of the Martial court, from the sittings between 26 March and 17 May 1919, the Trabzons Health Services Inspector Dr. Ziya Fuad wrote in a report that Dr. Saib caused the death of children with the injection of morphine. The information was allegedly provided by two physicians (Drs. Ragib and Vehib), both Dr. Saib's colleagues at Trabzons Red Crescent hospital, where those atrocities were said to have been committed.

On 11 July 1919, Damat Ferid Pasha (Grand Visier) officially confessed to massacres against the Armenians in the Ottoman Empire and was a key figure and initiator of the war crime trials held directly after World War I to condemn to death the chief perpetrators of the Genocide.

Article 230 of the Treaty of Sèvres required the Ottoman Empire to hand over to the Allied Powers the persons responsible for the massacres committed during the war on 1 August 1914.

On 15 March 1921, former Grand Vizier Talaat Pasha was assassinated in the Charlottenburg District of Berlin, Germany, in broad daylight and in the presence of many witnesses.

The Armenian Genocide took place before the coining of the term genocide. English-language words and phrases used by contemporary accounts to characterize the event include "massacres", "atrocities", "annihilation", "holocaust", "the murder of a nation", "race extermination" and "a crime against humanity". Raphael Lemkin coined "genocide" in 1943, with the fate of the Armenians in mind; he later explained that: "it happened so many times ... It happened to the Armenians, then after the Armenians Hitler took action".

In 2005, the International Association of Genocide Scholars affirmed that scholarly evidence revealed the "Young Turk government of the Ottoman Empire began a systematic genocide of its Armenian citizens – an unarmed Christian minority population. More than a million Armenians were exterminated through direct killing, starvation, torture, and forced death marches". The IAGS also condemned Turkish attempts to deny the factual and moral reality of the Armenian Genocide.

On 4 March 2010, a U.S. congressional panel narrowly voted that the incident was indeed genocide; within minutes the Turkish government issued a statement critical of "this resolution which accuses the Turkish nation of a crime it has not committed".

In late 2019, in the wake of the 2019 Turkish offensive into north-eastern Syria, both houses of United States Congress voted to officially recognize the Armenian Genocide, soon thereafter passing sanctions against Turkey.

As of 2021, 30 countries have recognized the genocide, along with Pope Francis and the European Parliament.