The Siege of Cuzco represents one of the major confrontations between Indigenous Incan forces and Spanish conquistadors during the Spanish conquest of the Inca Empire. The siege was initiated by Incan leaders, who rallied their people in a concerted effort to retake the city of Cuzco after the Spanish conquest had effectively dismantled their political structures and authority. Under the leadership of Manco Inca Yupanqui, the Inca sought to organize and mobilize their army to recover a city that held profound cultural and spiritual importance.

Cuzco, once the heart of the Inca Empire and its political center, had been largely controlled by the Spanish since their invasion led by Francisco Pizarro in the 1530s. The city's capture solidified Spanish dominance in the region and allowed for the establishment of colonial governance. However, Manco Inca aimed to reclaim this crucial city, launching assaults against the fortified positions maintained by the Spanish. The siege witnessed various tactics, including direct assaults and attempts to cut off supplies, illustrating the strategic ingenuity of the Indigenous forces.

The siege endured for several months as both sides faced significant challenges. The Spanish, while heavily outnumbered, benefited from superior weaponry and defensive structures. The Incan forces, motivated by the spirit of resistance, engaged in numerous skirmishes and assaults, but ultimately the siege highlighted the drastic power imbalance of the conquest. The failure to reclaim Cuzco did not diminish the Incan resolve but showcased the ongoing struggle against Spanish dominion and the significant cultural repercussions that would resonate for centuries to come.