Tetzcoco (Classical Nahuatl: Tetzco(h)co pronounced [tetsˈkoʔko], Otomi: Antamäwädehe) was a major Acolhua altepetl (city-state) in the central Mexican plateau region of Mesoamerica during the Late Postclassic period of pre-Columbian Mesoamerican chronology. It was situated on the eastern bank of Lake Texcoco in the Valley of Mexico, to the northeast of the Aztec capital, Tenochtitlan. The site of pre-Columbian Tetzcoco is now subsumed by the modern Mexican municipio of Texcoco and its major settlement, the city formally known as Texcoco de Mora. It also lies within the greater metropolitan area of Mexico City.

Pre-Columbian Tetzcoco is most noted for its membership in the Aztec Triple Alliance. At the time of the Spanish conquest of the Aztec Empire, it was one of the largest and most prestigious cities in central Mexico, second only to the Aztec capital, Tenochtitlan. A survey of Mesoamerican cities estimated that pre-conquest Tetzcoco had a population of 24,000+ and occupied an area of 450 hectares.

The people of Tetzcoco were called Tetzcocatl [tet͡sˈkokat͡ɬ] (singular) or Tetzcocah [tet͡sˈkokaʔ] (plural).

Tetzcoco was founded in the 12th century, on the eastern shore of Lake Texcoco, probably by the Chichimecs. In or about 1337, the Acolhua, with Tepanec help, expelled Chichimecs from Tetzcoco and Tetzcoco became the Acolhua capital city, taking over that role from Coatlinchan.

In 1418, Ixtlilxochitl I, the tlatoani (ruler) of Tetzcoco, was dethroned by Tezozomoc of Azcapotzalco. Ten years later, in 1428, Ixtlilxochitl's son, Nezahualcoyotl allied with the Mexica to defeat Tezozomoc's son and successor, Maxtla. Tetzcoco and the Aztecs of Tenochtitlan, with the Tepanecs of Tlacopan, subsequently formalized their association as the Triple Alliance. However this was an uneven alliance as Tlacopan entered the battle against Azcapotzalco late. Tetzcoco thereby became the second-most important city in the eventual Aztec empire, by agreement receiving two-fifths of the tribute collected while Tlacopan received one-fifth.

Tetzcoco was known as a center of learning within the empire, and had a famed library including books from older Mesoamerican civilizations.

Erected by the hill of Tetzcotzingo, the royal residence had aqueducts, baths, gardens, stairways and over 300 separate chambers.

The palace gardens were a vast botanical collection that included plants from not only the growing Aztec Empire but also the most remote corners of Mesoamerica. Remnants of the gardens still exist to this day and have recently been studied by a team of Discovery Channel scientists, who were able to demonstrate by means of modeling and computer simulation that the layout of the site had been carefully planned to be in alignment with astronomical events, with an emphasis on Venus, and not simply aligned with the cardinal directions as previously assumed.