Following the capture of Gallipoli by the Ottomans in 1354, Turkish expansion in the southern Balkans was rapid. The main target of the advance was Adrianople, which was the third most important Byzantine city (after Constantinople and Thessalonica). The date of Adrianople's fall to the Turks has been disputed among scholars due to the differing accounts in the source material. After the conquest, the city was renamed Edirne.The conquest of Adrianople was a turning point in the history of the Ottomans in Europe. Instead, the transformation of Adrianople into the new Ottoman capital of Edirne signalled to the local populace that the Ottomans intended to settle permanently in Europe.

The formation of the Janissaries has been dated to the reign of Murad I. The Ottomans instituted a tax of one-fifth on all slaves taken in war, and it was from this pool of manpower that the sultans first constructed the Janissary corps as a personal army loyal only to the sultan. From the 1380s to 1648, the Janissaries were gathered through the devşirme system, which was abolished in 1638. This was the taking (enslaving) of non-Muslim boys, notably Anatolian and Balkan Christians. Later, those from the territories what is now Albania, Bosnia, and Bulgaria were preferred.

By 1370 Murad controlled most of Thrace, bringing him into direct contact with Bulgaria and the southeastern Serbian lands ruled by Uglješa. Uglješa, the most powerful Serb regional ruler, unsuccessfully attempted to forge an anti-Ottoman alliance of Balkan states in 1371. Byzantium, vulnerable to the Turks because of its food supply situation, refused to cooperate. Bulgaria, following Ivan Aleksandar's death early that Year, lay officially divided into the "Empire" of Vidin, ruled by Stratsimir (1370–96), and Aleksandar's direct successor Tsar Ivan Shishman (1371–95), who ruled central Bulgaria from Turnovo. Young, his hold on the throne unsteady, threatened by Stratsimir, and probably pressured by the Turks, Shishman could not afford to participate in Uglješa's scheme. Of the regional Serb bojars, only Vukašin, protector of Uroš and Uglješa's brother, joined in the effort. The others either failed to recognize the Ottoman danger or refused to participate lest competitors attacked while they were in the field.

The Savoyard crusade was a crusading expedition to the Balkans in 1366–67. It was born out of the same planning that led to the Alexandrian Crusade and was the brainchild of Pope Urban V. It was led by Count Amadeus VI of Savoy and directed against the growing Ottoman Empire in eastern Europe. Although intended as a collaboration with the Kingdom of Hungary and the Byzantine Empire, the crusade was diverted from its main purpose to attack the Second Bulgarian Empire. There the crusaders made small gains that they handed over to the Byzantines. It did take back some territory the Ottomans in the vicinity of Constantinople and on Gallipoli.

Ugljesa, a Serbian despot realized the danger posed by the Ottoman turks who were getting close to his lands and tried to create a coalition against them. His idea was to drive them out of Europe instead of trying to defend fortresses and cities. The Serbian army numbered 50,000 –70,000 men. Despot Uglješa wanted to make a surprise attack on the Ottomans in their capital city, Edirne, while Murad I was in Asia Minor. The Ottoman army was much smaller, Byzantine Greek scholar Laonikos Chalkokondyles and different sources give the number of 800 up to 4,000 men, but due to superior tactics, by conducting a night raid on the Serbian camp, Şâhin Paşa was able to defeat the Serbian army and kill King Vukašin and despot Uglješa. Thousands of Serbs were killed, and thousands drowned in the Maritsa river when they tried to flee. After the battle, the Maritsa ran scarlet with blood.

After a 25-day-long siege the city fell to the Ottomans.

The Battle of Kosovo took place on 15 June 1389 between an army led by the Serbian Prince Lazar Hrebeljanović and an invading army of the Ottoman Empire under the command of Sultan Murad Hüdavendigâr. The army under Prince Lazar consisted of his own troops, a contingent led by Branković, and a contingent sent from Bosnia by King Tvrtko I, commanded by Vlatko Vuković. Prince Lazar was the ruler of Moravian Serbia and the most powerful among the Serbian regional lords of the time, while Branković ruled the District of Branković and other areas, recognizing Lazar as his overlord. There are different accounts from different sources about when and how Murad I was assassinated. The contemporary sources mainly noted that the battle took place and that both Prince Lazar and the Sultan lost their lives in the battle. One noteworthy detail of the battle is the first appearance of the Janissaries, who will feature in many more battles in the rise of the Ottoman Empire.

Murad established the sultanate by building up a society and government in the newly conquered city of Adrianople (Edirne in Turkish) and by expanding the realm in Europe, bringing most of the Balkans under Ottoman rule and forcing the Byzantine emperor to pay him tribute. It was Murad who established the former Osmanli tribe into an sultanate. He established the title of sultan in 1363 and the corps of the janissaries and the devşirme recruiting system. He also organised the government of the Divan, the system of timars and timar-holders (timariots) and the military judge, the kazasker. He also established the two provinces of Anadolu (Anatolia) and Rumeli (Europe).