During the Aztec rule, it was the market district of the Aztec capital Tenochtitlan, probably one of the largest in the Americas. According to Conquistador Bernal Diaz, it was larger than any market any of the Spaniards had seen, even those of Venice and Constantinople. When the conquistadors lead by Cortes lay siege to Tenochtitlan, and conquered and razed it district by district, the Aztecs, led by Cuauhtemoc, were finally confined to Tlatelolco, where they made their last stand, and were defeated and slaughtered by the conquistadors. Over 40,000 Aztec men, women, and children perished at Tlatelolco on August 13, 1521.
In 1967, the Treaty of Tlatelolco was opened for signature, with the aim of establishing a nuclear weapons-free zone throughout Latin America and the Caribbean. Since then, all the region's countries have signed and ratified the treaty.
The Nonoalco-Tlatelolco housing project is also home to the pyramid-shaped Banobras building, which houses a 47-bell carillon. At 125 m, this is the world's tallest carillon tower.