Lazar Hrebeljanović was a courtier at the court of Serbian Tsar Stefan Uroš Dušan, and at the court of Dušan's successor, Tsar Stefan Uroš V (r. 1356–1371). Uroš's reign was characterized by the weakening of the central authority and the gradual disintegration of the Serbian Empire. Powerful Serbian nobles became practically independent in the regions they controlled.

Lazar left the court Tsar Uroš in 1363 or 1365, and became a regional lord. He held the title of prince since at least 1371. His territory initially developed in the shadow of stronger regional lords. The strongest were the Mrnjavčević brothers, Vukašin and Jovan Uglješa. They were defeated and killed by the Ottoman Turks in the Battle of Maritsa in 1371, after which Lazar took a part of their territory.

Lazar and Tvrtko I, the Ban of Bosnia, jointly defeated in 1373 another strong noble, Nikola Altomanović. Most of Altomanović's territory was acquired by Lazar. About that time, Lazar accepted the suzerainty of King Louis I of Hungary, who granted him the region of Mačva, or at least a part of it. With all these territorial gains, Lazar emerged as the most powerful Serbian lord. The state he then created is known in historiography as the Principality of "Moravian Serbia".

Moravian Serbia attained its full extent in 1379, when Lazar took Braničevo and Kučevo, ousting the Hungarian vassal Radič Branković Rastislalić from these regions. Lazar's state was larger than the domains of the other lords on the territory of the former Serbian Empire. It also had a better organized government and army. The state comprised the basins of the Great Morava, West Morava, and South Morava Rivers, extending from the source of South Morava northward to the Danube and Sava Rivers. Its north-western border ran along the Drina River. Besides the capital Kruševac, the state included important towns of Niš and Užice, as well as Novo Brdo and Rudnik, two richest mining centres of medieval Serbia. Of all the Serbian lands, Lazar's state lay furthest from Ottoman centres, and was least exposed to the ravages of Turkish raiding parties. This circumstance attracted immigrants from Turkish-threatened areas, who built new villages and hamlets in previously poorly inhabited and uncultivated areas of Moravian Serbia. There were also spiritual persons among the immigrants, which stimulated the revival of old ecclesiastical centres and the foundation of new ones in Lazar's state.

After the death of King Louis in 1382, a civil war broke out in the Kingdom of Hungary. Lazar briefly participated in the war as one of the opponents of Prince Sigismund of Luxemburg, and he sent some troops to fight in the regions of Belgrade and Syrmia. These fights ended with no territorial gains for Lazar, who made peace with Sigismund in 1387.

The Ottoman army penetrated Pomoravlje and neighbouring areas, killing and looting, then clashed with the subjects of Lazar at Dubravnica (1381), where they were successfully fought off. With a larger force, the Ottoman Sultan Murad I attacked Serbia in 1386, when according to some sources Niš was conquered. The Serbian army emerged victorious, although details of the actual battle are scarce. The victory gave prestige to the Serbs. It was the first serious defeat of the Ottomans in the Balkans.

The Ottoman army campaigned in Bosnia, fighting the troops of the Kingdom of Bosnia led by Grand Duke Vlatko Vuković and Radič Sanković at Bileća, ending in a decisive Bosnian victory. From this the Ottomans learned how to fight against heavy cavalry. This became valuable experience for the Battle of Kosovo.

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 battle was fought on the Kosovo field in the territory ruled by Serbian nobleman Vuk Branković, in what is today Kosovo, about 5 kilometers (3.1 mi) northwest of the modern city of Pristina. 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. Reliable historical accounts of the battle are scarce.

The bulk of both armies were wiped out, and Lazar and Murad were killed. Both armies were effectively wiped out, however, Serbian manpower was depleted and had no capacity to field large armies against future Ottoman campaigns, which relied on new reserve forces from Anatolia. Consequently, the Serbian principalities that were not already Ottoman vassals, became so in the following years.

Stefan Lazarević was the son of Prince Lazar Hrebeljanović. He was regarded as one of the finest knights and military leaders at that time. After the death of his father at Kosovo (1389), he became ruler of Moravian Serbia and ruled with his mother Milica (a Nemanjić), until he reached adulthood in 1393. Stefan led troops in several battles as an Ottoman vassal, until asserting independence after receiving the title of despot from the Byzantines in 1402.

Becoming a Hungarian ally in 1403–04, he received large possessions, including the important Belgrade and Golubac Fortress. He also held the superior rank in the chivalric Order of the Dragon. During his reign there was a long conflict with his nephew Đurađ Branković, which ended in 1412. Stefan also inherited Zeta, and waged war against Venice. Since he was childless, he designated his nephew Đurađ as heir in 1426, a year before his death.

On the domestic front, he broke the resistance of the Serbian nobles, and used the periods of peace to strengthen Serbia politically, economically, culturally and militarily. In 1412 he issued the Code of Mines, with a separate section on governing of Novo Brdo – the largest mine in the Balkans at that time. This code increased the development of mining in Serbia, which had been the main economic backbone of the Serbian Despotate. At the time of his death, Serbia was one of the largest silver producers in Europe. In the field of architecture, he continued development of the Morava school. His reign and personal literary works are sometimes associated with early signs of the Renaissance in the Serbian lands. He introduced knightly tournaments, modern battle tactics, and firearms to Serbia. He was a great patron of the arts and culture by providing shelter and support to scholars and refugees from neighboring countries that had been taken by the Ottomans. In addition, he was himself a writer, and his most important work is A Homage to Love, which is characterized by the Renaissance lines. During his reign the Resava School was formed.

Lazar was succeeded by his eldest son Stefan Lazarević. As he was still a minor, Moravian Serbia was administered by Lazar's widow, Milica. She was attacked from north, five months after the battle, by troops of the Hungarian King Sigismund. When Turkish forces, moving toward Hungary, reached the borders of Moravian Serbia in the summer of 1390, Milica accepted Ottoman suzerainty.

After the battle, in 1390 or 1391 depending on source, Serbia became a vassal Ottoman state, and Stefan Lazarević was obliged to participate in battles if ordered by the Ottoman sultan. He did so in the Battle of Karanovasa in 1394, in the Battle of Rovine in May 1395 against the Wallachian prince Mircea I and the Battle of Nicopolis in 1396 against the Hungarian king Sigismund. After that, Sultan Bayezid awarded Stefan with the majority of the Vuk Branković's land on Kosovo, as Branković sided with the Hungarian king at Nicopolis.

The Battle of Ankara was fought between the forces of the Ottoman Sultan Bayezid I and the Emir of the Timurid Empire, Timur. The battle was a major victory for Timur, and it led to the Ottoman Interregnum.

After Ankara, Stefan Lazarević visited Constantinople, the capital city of the Byzantine Empire, where he was given the title of Despot, and since then his state became known as the Serbian Despotate in 1402.

Stefan had a quarrel with his brother Vuk Lazarević, who went to the Ottoman side, to the new sultan (actually co-ruler with his three brothers) Suleyman (I) Çelebi. Counting on unrest within the Ottoman Empire (Ottoman Interregnum), in early 1404 Stefan accepted vassalage to the Hungarian king Sigismund, who awarded him with Belgrade, the Mačva region, and the fort of Golubac, until then in possession of the Kingdom of Hungary, so Belgrade became a capital of Serbia for the second time in history after King Dragutin. He managed to liberate his sister and Bayezid's widow Olivera. In 1404 he made peace with his brother Vuk, in 1405 he married Caterina Gattilusio, daughter of Francesco II Gattilusio, ruler of the island of Lesbos. Also in 1405 his mother Milica died.

In 1410 King Sigismund of Hungary seized several territories in north-eastern Bosnia. As a reward for Stefan Lazarević's help and loyalty, he transferred Srebrenica with its surroundings to the Serbian Despotate in 1411 or 1412.

When Musa became self-proclaimed sultan in European part of the Ottoman Empire, he attacked Serbia in early 1412 but was defeated by Stefan near Novo Brdo in Kosovo. Stefan then invited the ruler of the Anatolian part of the empire, sultan Mehmed Çelebi to attack Musa together. Securing Hungarian help, they attacked Musa on 5 July 1413 at the Battle of Çamurlu, near the Vitosha mountain (modern Bulgaria) and defeated him, with Musa being killed in the battle. As a reward, Stefan received the town of Koprijan near Niš and the Serbian-Bulgarian area of Znepolje. For next twelve years, Stefan remained in good relations with Mehmed, which made the recovery of medieval Serbia possible.

In 1425, the Ottoman Empire invaded Serbia, burning and pillaging across the Southern Morava valley. At the same time, the King of Bosnia attempted to conquer Srebrenica back from the Serbs, but failed. Despot Stefan fought back the invasion and initiated negotiations with the Sultan, after which the Ottoman troops left Serbia. Still, this attack was an ominous sign of things to come.

As despot Stefan had no children of his own, already in 1426 he bequeathed the Despotate to his nephew, Đurađ Branković, who succeeded him upon his death on July 19, 1427. Already the second most important figure in the Despotate for the last 15 years, he was confirmed as despot by the Byzantine emperor John VIII Palaeologus in 1429.

As an immediate result of Stefan's death, Serbia had to return Belgrade to the Kingdom of Hungary, but kept Mačva. As the southern wealthy cities (like Novo Brdo) were too close to the Ottomans to be declared new capitals, Đurađ decided to build a new one, the magnificent fortress of Smederevo on the Danube, close to the border of the Kingdom of Hungary.

The Battle of Zlatitsa was fought on 12 December 1443 between the Ottoman Empire and Serbian Hungarian troops in the Balkans. The battle was fought at Zlatitsa Pass near the town of Zlatitsa in the Balkan Mountains, Ottoman Empire (modern-day Bulgaria). The impatience of the king of Poland and the severity of the winter then compelled Hunyadi (February 1444) to return home, but not before he had utterly broken the Sultan's power in Bosnia, Herzegovina, Serbia, Bulgaria, and Albania.

The Second Battle of Kosovo was a land battle between a Hungarian-led Crusader army and the Ottoman Empire at Kosovo Polje. It was the culmination of a Hungarian offensive to avenge the defeat at Varna four years earlier. In the three-day battle the Ottoman army under the command of Sultan Murad II defeated the Crusader army of regent John Hunyadi. After that battle, the path was clear for the Turks to conquer Serbia and the other Balkan States, it also ended any hopes of saving Constantinople. The Hungarian kingdom no longer had the military and financial resources to mount an offensive against the Ottomans. With the end of the half-century-long Crusader threat to their European frontier, Murad's son Mehmed II was free to lay siege to Constantinople in 1453.

After the fall of Constantinople in 1453, the Ottoman Sultan Mehmed the Conqueror rallied his resources to subjugate the Kingdom of Hungary. Without formally declaring an end to the peace treaty, Sultan Mehmed II invaded Serbia in mid-July 1454. His immediate objective was the border fort of the town of Belgrade. Much of central Serbia fell, but the capital was well-prepared and the Ottomans, upon hearing that Hunyadi would cross the Danube to reinforce the Serbs, soon lifted their siege of Smederevo. The Sultan retreated back to Sofia with loot and slaves, leaving most of his army at Kruševac.

During the Ottoman invasion, two Serbian armies were set up to defend the Despotate, with the 1st army being commanded by Nikola Skobaljić in Dubočica, near Leskovac, and the 2nd army being on the banks of Sitnica River in Kosovo.

An initial invading Ottoman force heading from Sofia cut off Skobaljić's army from Serbia's north. Despot Đurađ Branković suggested that Skobaljić either surrender, or hide from the Ottoman army until John Hunyadi was able to reinforce or liberate the trapped half of the Serbian army, which would render the Ottomans to pillage and raze the rich southern part of the despotate with no resistance. The young voivode disobeyed the despot, and the invading Ottoman army coming from Macedonia was met by Nikola Skobaljić near Banja. The Serbs scored a decisive victory against the Ottoman army, employing guerrilla tactics.

The Battle of Kruševac was fought on October 2, 1454 between the forces of the Serbian Despotate, allied with the Kingdom of Hungary, and the Ottoman Empire.

In 1454 the Ottomans launched a major invasion against Serbia, at the helm of which was the Sultan himself, Mehmed the Conqueror. Initially, Serbs led by Nikola Skobaljić scored a decisive victory a month earlier near Leskovac, surprising a much larger Ottoman army. On the Morava River, Sultan Mehmed II left Feriz Bey and 32,000 of his troops to resist any possible counterattacks by the Serbs south of Kruševac. The Serbs did not hesitate to make the first move and the two armies met.

The victory at Leskovac allowed John Hunyadi and Đurađ Branković to decisively strike at the isolated Turkish army, and launch a major offensive, ravaging Niš and Pirot, and burning down Vidin. Nikola Skobaljić continued his forays against the Ottomans, operating between Leskovac and Priština, and won several major victories against the armies of the sultan.

The Siege of Belgrade, one of the greatest crusade wars of medieval times takes place in Belgrade as Sultan Mehmed II besieges the city with 150,000 soldiers and over 100 ships. Joint Hungarian and Serbian troops, aided by other Christian nations, repel the Ottoman forces. Pope Calixtus III praises Belgrade and its defender John Hunyadi as the Saviors of Christianity. Catholic Belgrade is now the only bastion of Christianity in the Balkans.

Despot Lazar Branković, the only one of Đurađ's sons not to be blinded by the Ottomans, succeeded his father. Sensing that Serbia is too weak to defeat a future Ottoman incursion on the battlefield, he managed to make a deal with sultan Mehmed II on January 15, 1457. According to this deal, he was granted back most of his father's lands and a promise that Serbia will not be disturbed by the Ottomans until Lazar's death. Lazar in turn had to pay a tribute, which was reduced because he no longer had the rich mines of Novo Brdo. Temporarily relieved of the southern threat, Lazar turned to the north and Hungarian internal battles, which he joined on the side of King Ladislaus, managing to capture the town of Kovin and several other towns on the left bank of the Danube in 1457. Lazar suddenly died on January 20, 1458.

During the chaos that surrounded Lazar's death and the split in the provisional regency, King Stjepan Tomaš of Bosnia attacked the Despotate's holdings west of the Drina river and conquered most of them, leaving only Teočak in the Despotate's hands. Mihail Silagyi likewise seized most of Lazar's towns north of the Danube. Immediately after Mihailo Anđelović's failed coup, the Ottomans began another invasion of Serbia. Although they would not make any significant territorial gains until 1459, this was the beginning of the end for the Serbian Despotate. Stefan Branković ruled until 8 April 1459, when he was overthrown by a plot between Helena Palaiologina and King Tomaš, whose son briefly ruled as the new Despot.

Stjepan Tomašević lost two countries to the Ottomans: Serbia in 1459 and Bosnia in 1463. His appointment as new despot was highly unpopular but pushed hard by his father, King Stjepan Tomaš of Bosnia. By this time Serbia was reduced to only a strip of land along the Danube. Sultan Mehmed II decided to conquer Serbia completely and arrived at Smederevo; the new ruler did not even try to defend the city. After negotiations, Bosnians were allowed to leave the city and Serbia was officially conquered by Turks on June 20, 1459.

The Hungarian rulers renewed the legacy of Despots to the House of Branković in exile, later to the noble family of Berislavići Grabarski, who continued to govern most of Syrmia until the Ottoman conquest but territory has been in theory still under administration of the medieval Kingdom of Hungary.