The Spanish assault on the Aztec Empire in 1519 represented the second major stage of Spanish expansion in the Americas. The first stage had established permanent settlements in the Caribbean Sea, including the city of Santo Domingo (now the capital of the Dominican Republic) and outposts on the island of Cuba. These settlements made it possible for the Spaniards to probe the mainland of Mexico and Central America knowing that they could quickly return to their island outposts.
The first governor of Cuba, Diego Velázquez, sponsored three expeditions in the early 1500s that sought to explore the Gulf Coast of Mexico. The first expedition, commanded by Spanish navigator and conqueror Francisco Hernández de Córdoba, set sail from Cuba in 1517 and explored uncharted territory along the Yucatán Peninsula. When Spanish soldiers went ashore to seek water and food they were often attacked by Maya warriors. The Spaniards and the Maya engaged in a major battle in Champóton, now a port in the modern state of Campeche. More than half the Spanish expedition was killed. While the expedition ended in failure, it provided the Spaniards with more detailed knowledge of the native inhabitants of the region and sparked new interest in Mexico.

In 1518 Governor Velázquez sponsored another expedition, this time under the command of his nephew, Juan de Grijalva. The Spaniards returned to Champóton, where they avenged the defeat of the previous expedition, forcing the Maya to retreat inland after three days of fierce fighting. The expedition continued exploring the Gulf Coast, eventually encountering friendly Mayan-speaking peoples who told the Spaniards of a powerful empire to the west. Although the Spaniards did not realize it, they had reached the outer limits of the Aztec Empire.

The ruler of the Aztec Empire at this time, Montezuma II, had received reports of the Spanish explorations, as well as the battles at Champóton. He ordered his subjects along the Gulf Coast to greet the foreigners, offer them a large feast and gifts of gold and jewelry, and then ask them to leave the region. Montezuma knew of the Aztec legends and omens predicting future destruction, and is reported to have wondered whether the arrival of the Europeans heralded the return of an angry Quetzalcoatl.

Grijalva returned to Cuba and relayed to Governor Velázquez the tales of a powerful and wealthy Native American empire located in the interior of Mexico. This news spurred Velázquez to authorize a third expedition, this time commanded by Hernán Cortés.

As Cortés loaded his ships and recruited additional men in Cuba, some of his enemies complained that he was a poor choice to lead the expedition. They convinced Velázquez to cancel Cortés's commission to lead the force. Cortés ignored the orders and set sail in February 1519 with about 600 men, as well as a few cannons and horses. On the Yucatán Peninsula, the expedition rescued a shipwrecked survivor, Jerónimo de Agúilar, who had been held captive by the Maya for eight years. Upon meeting the Spaniards, Aguilar refused to go with them explaining that he preferred to remain with the Maya. The Spaniards nonetheless forced him to join their expedition and he would provide them with a valuable translator of the Mayan language.

The expedition sailed west along the Yucatán Peninsula and the Gulf Coast, engaging in a major battle against Tabascan warriors at the mouth of the Grijalva River. Cortés quickly realized the value of horses in battling the Native American peoples-the Tabascans had never seen horses and many fled in fear. The expedition sailed north in search of a good harbor and established a town, La Villa Rica de la Vera Cruz, at what is now the city of Veracruz. Cortés organized an independent government, renounced the authority of Governor Velázquez, and acknowledged only the supreme authority of the Spanish Crown. In order to prevent any of his men from deserting because of these actions, Cortés destroyed his fleet.

When Cortés started to march inland he had about 500 men remaining. The Spaniards soon encountered the Tlaxcalan people, who lived east of the Aztec Empire and resented Aztec domination. Despite this resentment, the Tlaxcalans initially battled the Spanish invaders. After two weeks of fighting and heavy native losses, the Tlaxcalans surrendered and became allies of the Spaniards against the Aztecs. Until the conquest was achieved in 1521, the Tlaxcalans were important allies of the Spaniards and helped create a combined European/Native American army that numbered in the thousands.

In October 1519 the Spaniards and several thousand of their Tlaxcalan allies marched into Cholula, an ancient city devoted to the god Quetzalcoatl. Cholulan priests and leaders welcomed the Spaniards but demanded that the Tlaxcalans camp outside the city. After three days in the city, the Spaniards were informed of an impending ambush. Cortés reacted by summoning all the nobles of Cholula and locking them in a room, which left the Cholulans leaderless. The Spaniards, with the assistance of the Tlaxcalans, then massacred many of the city's residents, killing more than 3,000 people in all.

As the Spaniards subdued the region around Cholula and began exploring the road to the Aztec capital, an increasingly desperate Montezuma decided not to oppose the invaders. Although about 4,000 Tlaxcalans accompanied the Spaniards as they marched toward Tenochtitlán, the combined force was still relatively small and vastly outnumbered by the Aztec warriors. On November 8, 1519, Cortés met Montezuma outside the city, the two leaders politely greeted each other, and the Aztecs led the Spaniards into their city. The Spanish soldiers established a headquarters in a large communal dwelling and were allowed to roam through the city, where they found much gold and other treasures in Aztec storehouses.

Despite the friendly reception given the Spaniards, Cortés believed that the Aztecs would attempt to drive him out. To safeguard his position, he seized Montezuma as a hostage and forced him to swear allegiance to the king of Spain, Charles I, and to provide an enormous ransom in gold and jewels. Over the next several months the Spaniards began devising strategies to conquer the entire region.

Meanwhile, Governor Velázquez had dispatched an expedition to Mexico to arrest Cortés and return him to Cuba. In April 1520 Cortés received word that the expedition had arrived on the Gulf Coast. Leaving 200 men at Tenochtitlán under the command of Pedro de Alvarado, Cortés marched with a small force to the coast. He entered the Spanish camp at night, captured the leader, and induced the majority of the Spaniards to join his force.

In Tenochtitlán, Alvarado feared an Aztec attack and instituted a number of harsh rules while Cortés was absent from the city. When Alvarado's men attacked and killed hundreds of worshippers at a religious ceremony, the city's outraged population revolted and besieged the Spaniards in the building where Montezuma was still being held prisoner. The revolt was underway when Cortés returned to the city.

Cortés and his men, as well as 3,000 Tlaxcalan allies, were allowed to enter the city and join Alvarado, but they were immediately surrounded and attacked. At Cortés's request, Montezuma addressed the Aztecs in an attempt to quell the revolt. The Aztec ruler was stoned by his people, and he died three days later. Immediate retreat from the city appeared to be the Spaniards' only option for survival. On June 30, 1520-a rainy night that became known as the Noche Triste ("Sad Night")-the Spaniards attempted a panicked retreat. Fleeing across a causeway, they were chased by Aztec warriors and attacked on both sides by Aztecs in canoes. More than half the Spaniards were killed, all of their cannons were lost, and most of the treasure they attempted to carry out was abandoned or lost in the lake and canals. The Aztecs pursued the retreating Spanish troops, but the survivors of the Noche Triste managed to find refuge in Tlaxcala.

During the summer of 1520, Cortés reorganized his army in Tlaxcala with the aid of reinforcements and equipment from Veracruz. He then began his return to the capital, capturing Aztec outposts along the way, and subduing Aztec settlements around Lake Texcoco. By May 1521 the island capital of Tenochtitlán was isolated and surrounded by the Spaniards. Spanish artillery mounted on ships specially constructed for the shallow lake bombarded Tenochtitlán. Spanish soldiers launched daily attacks on the city, whose supplies of food and fresh water had been cut. Famine, dysentery, and smallpox ravaged the Aztec defenders. On August 13, 1521, after a desperate siege of three months, Cuauhtémoc, the new emperor, was captured and Tenochtitlán fell. More than 40,000 decomposed bodies littered the destroyed city and bloated corpses floated in canals and the lake. A fabulous city and its empire had been destroyed.