The Safavid dynasty had ruled Persia since 1501, building Isfahan into one of the world's great cities. By the early 18th century, however, the empire was rotting from the top. Successive shahs showed little interest in governing. Royal intrigues consumed the court. The Qizilbash military establishment and provincial governors competed for power with little central oversight. Recurrent wars with the Ottomans drained the treasury and exhausted the army. In the empire's eastern provinces, the Safavid commitment to Shia Islam translated into severe oppression of Sunni Pashtuns. The Pashtun rebellion that Mir Wais Hotak launched was not a bolt from the sky. It was the inevitable fracture point of an empire that had stopped paying attention to its own subjects. Punitive campaigns sent from Isfahan to crush the revolt were defeated one after another. When Mir Wais died in 1715, his son Mahmud inherited both his father's army and his cause.

On March 8, 1722, the Afghan and Persian armies met at the Battle of Gulnabad, just outside Isfahan. Mahmud Hotak commanded roughly 18,000 troops. The Safavid army fielded around 40,000. Numbers should have decided the contest, but the Safavid forces were poorly led and badly coordinated. The Afghans won a decisive victory, and the Persian army fell back to Isfahan in disarray. What followed was not a dramatic storming of the walls. Mahmud lacked the artillery to breach Isfahan's fortifications. Instead, he surrounded the city and waited. The siege became a slow strangulation. Safavid attempts to organize relief failed. Shah Sultan Hussayn appealed to his Georgian vassal, Vakhtang VI of Kartli, for military support. Vakhtang refused. The shah's son, Tahmasp, managed to slip out of the city with about 600 soldiers, hoping to raise a relief army from the provinces, but help never arrived in time.

Inside the walls, Isfahan starved. The city that Shah Abbas I had rebuilt as the jewel of the Persian world, with its grand squares, its mosques clad in blue tile, its gardens fed by the Zayandeh River, became a trap. The population that had thrived under Safavid patronage now watched food supplies dwindle to nothing. Famine spread through the streets. The suffering was not abstract: these were merchants who had traded silk along routes stretching to India and Europe, artisans who had tiled the Shah Mosque, scholars who had studied in the city's madrasas. Eight months of blockade reduced them to desperation. On October 23, 1722, Shah Sultan Hussayn capitulated. He abdicated in favor of Mahmud Hotak, who entered the city triumphantly two days later, on October 25. The Safavid dynasty, which had shaped Persian identity for over two centuries, effectively ended in that act of surrender.

The fall of Isfahan sent shockwaves far beyond Persia. Russia and the Ottoman Empire, sensing opportunity in Safavid weakness, moved to seize Persian territory. In 1724, the two powers signed the Treaty of Constantinople, dividing northern Iran between them. Russia's Peter the Great wanted a trade route to India through the lands east of the Caspian Sea. The Ottomans wanted to keep Russia at a safe distance from their own borders. The Afghan rulers who succeeded Mahmud, particularly his cousin Ashraf, tried to consolidate power. In 1727, Ashraf ceded western Iran to the Ottomans in exchange for recognition as ruler. Most of the Safavid princes and the deposed Shah Sultan Hussayn were executed under Afghan rule. The dynasty's bloodline was being systematically erased.

The Safavid story did not end entirely in 1722. Shah Sultan Hussayn's son, Tahmasp II, the prince who had escaped the siege, eventually found his general: Tahmasp Qoli Khan, a military commander of extraordinary ability who would later take the name Nader Shah. In 1729, their combined forces defeated the Afghan army in three battles and drove Ashraf from Isfahan. Ashraf was killed by his own followers while fleeing, ending seven years of Afghan control over Persia. Nader restored the Safavid political system under Tahmasp II, but the restoration was a prelude to his own ambitions. By 1736, Nader had deposed Tahmasp's young son Abbas III and proclaimed himself shah, founding the Afsharid dynasty. The siege of Isfahan thus set in motion a chain of events that reshaped not just Persia but the entire region, replacing one fallen dynasty not with its conquerors but with a general who used the chaos to build an empire of his own.