The Tlaxcaltecas were the sixth of the seven lineages that left Chicomostoc (place of the seven caves), arriving in the plains of Poyoauhtlan in the year 1208.

In those plains, located between the current towns of Texcoco and Chimalhuacán in the state of Mexico, they fought against the Tepanecas and emerged victorious.

Around 1350, they left the plains of Poyoauhtlán, dividing into two groups: one group traveled north to Texcoco, reaching the territory of the current state of Hidalgo, where they founded Tulancingo and Huauchinango, while the other group crossed the Sierra Nevada through Amecameca and, skirting the slopes of the Popocatepetl volcano, passed through Huejotzingo and Cholula, finally arriving at Contla and then Tepectipac in the year 1380, where they founded the first lordship.

Colonial Era

When Hernán Cortés requested permission from the Tlaxcaltecan lords to pass through their territory on his way to Tenochtitlán, through the embassy of four Cempoaltecas leaders, the main opposition to allowing them to pass came from the warrior Xicohténcatl Axayacatzin, son of the lord of Tizatlán, Xicohténcatl Huehuetl.

Axayacatzin argued before the Tlaxcaltecan rulers that the prophecy of the arrival of the fair-skinned and bearded men - related to the return of Quetzalcóatl - could be a deception and that those eastern walkers might not be the ones they were expecting. He also said, "the floating castles were a result of human work, admired because they had not seen them before," and proposed to the four lords "to see the foreigners as tyrants of the homeland and the gods." This speech, contrary to the opinion of Maxixcatzin, lord of Ocotelulco, decided the confrontations with the Spaniards.

Cortés entered the territory of Tlaxcala through the ravine now known as La Mancera. The first confrontations between the Spanish and the Tlaxcaltecas occurred in Tecoac. In September 1519, the troops of Xicohténcatl fought against those of Cortés in the Tecoatzingo gorge, with adverse results for the Tlaxcaltecas. The next day, they fought on the plains of the same place, once again without achieving victory.

The defection of the divisions of Ocotelulco and Tepetícpac, due to the intrigues of Maxixcatzin, weakened the forces of Captain Xicohténcatl. Believing that the fair-skinned men gained strength with the support of the sun, he attempted to defeat them in a nocturnal joust, which also turned out to be unsuccessful.

Upon learning of this last defeat, the Tlaxcaltecan lords decided to offer peace to Cortés, ordering Xicohténcatl Axayacatzin to suspend hostilities. The peace was made on the hill of Tzompantepec in the same September of 1519, on the terms of a friendly alliance.

Although the military alliance with the Spaniards gave the Tlaxcaltecas exceptional cohesion and cultural identity compared to the conquered peoples who would later form New Spain, it should be noted that the Tlaxcaltecan lords were not the first or only ones to negotiate with the Spaniards on the terms of joining the conquest of Tenochtitlán.

Aun cuando esa unión militar con los españoles dio a los tlaxcaltecas una cohesión e identidad cultural de carácter excepcional respecto de los pueblos conquistados que más tarde configurarían la Nueva España, debe señalarse que los señores tlaxcaltecas no fueron ni los primeros, ni los únicos en negociar con los españoles los términos en que marcharían juntos a la conquista de Tenochtitlán.

Once peace was established, Cortés arrived with his army in Tizatlán on September 23, 1519, and stayed at the house of Xicohténcatl. For 20 days, he rested in the territory of Tlaxcala, where the daughters of chiefs and governors were offered to him as gifts, and they received baptism and the new religion.

The advantages of the Hispanic-Tlaxcaltecan alliance were soon felt with the massacre of the nobility in Cholula. This pillage provided the Tlaxcaltecas, apart from the expected revenge, with salt, gold, cotton, and other articles that they had been deprived of due to the blockade.

The foundation of the city was carried out to consolidate the alliance with the four lordships, bringing them together by congregating the leaders and their subjects. This introduced the religious, governmental, and social institutions of the conquerors, gradually replacing those of the indigenous people.

Once the occupation of New Spain was consolidated, it was divided into five major provinces, one of which was Tlaxcala. The city itself was erected between 1540 and 1549, during the Viceroyalty of New Spain, under the administration of Antonio de Mendoza. The Franciscan friars played an active role in the city's layout. The province was governed by a mayor, who had four senators from Tlaxcala under his authority.

In the late 16th century, the Spanish government elevated the mayoralty to a governorship with powers to exercise acts of justice.

It was not until 1524 when the formal Franciscan evangelization project began in Tlaxcala. However, the evangelizing work undertaken by the Franciscans was not easy, as the resistance to the conversion of the Tlaxcaltecas often resulted in deaths.