Chiapas, as the southernmost state of Mexico, has had unique interactions with both Central America and the rest of Mexico throughout much of its history.

Pre-Columbian era Hunter gatherers began to occupy the central valley of the state around 7000 BCE, but little is known about them. The oldest archaeological remains in the seat are located at the Santa Elena Ranch in Ocozocoautla whose finds include tools and weapons made of stone and bone. It also includes burials.Jiménez González, p. 29. In the pre Classic period from 1800 BCE to 300 CE, agricultural villages appeared all over the state although hunter gather groups would persist for long after the era.

Recent excavations in the Soconusco region of the state indicate that the oldest civilization to appear in what is now modern Chiapas is that of the Mokaya, which were cultivating corn and living in houses as early as 1500 BCE, making them one of the oldest in Mesoamerica.Jiménez González, p. 35. There is speculation that these were the forefathers of the Olmec, migrating across the Grijalva Valley and onto the coastal plain of the Gulf of Mexico to the north, which was Olmec territory. One of these people's ancient cities is now the archeological site of Chiapa de Corzo, in which was found the oldest calendar known on a piece of ceramic with a date of 36 BCE. This is three hundred years before the Mayans developed their calendar. The descendants of Mokaya are the Mixe-Zoque.

During the pre Classic era, it is known that most of Chiapas was not Olmec, but had close relations with them, especially the Olmecs of the Isthmus of Tehuantepec. Olmec-influenced sculpture can be found in Chiapas and products from the state including amber, magnetite, and ilmenite were exported to Olmec lands. The Olmecs came to what is now the northwest of the state looking for amber with one of the main pieces of evidence for this called the Simojovel Ax.

Mayan civilization began in the pre-Classic period as well, but did not come into prominence until the Classic period (300–900 CE). Development of this culture was agricultural villages during the pre-Classic period with city building during the Classic as social stratification became more complex. The Mayans built cities on the Yucatán Peninsula and west into Guatemala. In Chiapas, Mayan sites are mostly concentrated along the state's borders with Tabasco and Guatemala, near Mayan sites in those entities. Most of this area belongs to the Lacandon Jungle.Jiménez González, pp. 29–30.

Mayan civilization in the Lacandon area is marked by rising exploitation of rain forest resources, rigid social stratification, fervent local identity, waging war against neighboring peoples. At its height, it had large cities, a writing system, and development of scientific knowledge, such as mathematics and astronomy. Cities were centered on large political and ceremonial structures elaborately decorated with murals and inscriptions. Among these cities are Palenque, Xupa, Bonampak, Lacanha, Yaxchilan, Chinkultic, Toniná, Chinikiha, El Cayo, La Mar, El Palma, Oxlahuntun and Sak Tz'i. The Mayan civilization had extensive trade networks and large markets trading in goods such as animal skins, indigo, amber, vanilla and quetzal feathers. It is not known what ended the civilization but theories range from over population size, natural disasters, disease, and loss of natural resources through over exploitation or climate change.

Nearly all Mayan cities collapsed around the same time, 900 CE. From then until 1500 CE, social organization of the region fragmented into much smaller units and social structure became much less complex. There was some influence from the rising powers of central Mexico but two main indigenous groups emerged during this time, the Zoques and the various Mayan descendants. The Chiapans, for whom the state is named, migrated into the center of the state during this time and settled around Chiapa de Corzo, the old Mixe–Zoque stronghold. There is evidence that the Aztecs appeared in the center of the state around Chiapa de Corza in the 15th century, but were unable to displace the native Chiapa tribe. However, they had enough influence so that the name of this area and of the state would come from Nahuatl.

Colonial era

When the Spanish arrived in the 16th century, they found the indigenous peoples divided into Mayan and non-Mayan, with the latter dominated by the Zoques and Chiapanecas. The first contact between Spaniards and the people of Chiapas came in 1522, when Hernán Cortés sent tax collectors to the area after Aztec Empire was subdued. The first military incursion was headed by Luis Marín, who arrived in 1523. After three years, Marín was able to subjugate a number of the local peoples, but met with fierce resistance from the Tzotzils in the highlands. The Spanish colonial government then sent a new expedition under Diego de Mazariegos. Mazariegos had more success than his predecessor, but many natives preferred to commit suicide rather than submit to the Spanish. One famous example of this is the Battle of Tepetchia, where many jumped to their deaths in the Sumidero Canyon.

Indigenous resistance was weakened by continual warfare with the Spaniards and disease. By 1530 almost all of the indigenous peoples of the area had been subdued with the exception of the Lacandons in the deep jungles who actively resisted until 1695. However, the main two groups, the Tzotzils and Tzeltals of the central highlands were subdued enough to establish the first Spanish city, today called San Cristóbal de las Casas, in 1528. It was one of two settlements initially called Villa Real de Chiapa de los Españoles and the other called Chiapa de los Indios.

Soon after, the encomienda system was introduced, which reduced most of the indigenous population to serfdom and many even as slaves as a form of tribute and way of locking in a labor supply for tax payments. The conquistadors brought previously unknown diseases. This, as well as overwork on plantations, dramatically decreased the indigenous population. The Spanish also established missions, mostly under the Dominicans, with the Diocese of Chiapas established in 1538 by Pope Paul III. The Dominican evangelizers became early advocates of the indigenous' people's plight, with Bartolomé de las Casas winning a battle with the passing of a law in 1542 for their protection. This order also worked to make sure that communities would keep their indigenous name with a saint's prefix leading to names such as San Juan Chamula and San Lorenzo Zinacantán. He also advocated adapting the teaching of Christianity to indigenous language and culture.

The encomienda system that had perpetrated much of the abuse of the indigenous peoples declined by the end of the 16th century, and was replaced by haciendas. However, the use and misuse of Indian labor remained a large part of Chiapas politics into modern times. Maltreatment and tribute payments created an undercurrent of resentment in the indigenous population that passed on from generation to generation. One uprising against high tribute payments occurred in the Tzeltal communities in the Los Alto region in 1712. Soon, the Tzoltzils and Ch'ols joined the Tzeltales in rebellion, but within a year the government was able to extinguish the rebellion.

As of 1778, Thomas Kitchin described Chiapas as "the metropolis of the original Mexicans," with a population of approximately 20,000, and consisting mainly of indigenous peoples. The Spanish introduced new crops such as sugar cane, wheat, barley and indigo as main economic staples along native ones such as corn, cotton, cacao and beans. Livestock such as cattle, horses and sheep were introduced as well. Regions would specialize in certain crops and animals depending on local conditions and for many of these regions, communication and travel were difficult. Most Europeans and their descendants tended to concentrate in cities such as Ciudad Real, Comitán, Chiapa and Tuxtla. Intermixing of the races was prohibited by colonial law but by the end of the 17th century there was a significant mestizo population. Added to this was a population of African slaves brought in by the Spanish in the middle of the 16th century due to the loss of native workforce.Jiménez González, pp. 30–31.

Initially, "Chiapas" referred to the first two cities established by the Spanish in what is now the center of the state and the area surrounding them. Two other regions were also established, the Soconusco and Tuxtla, all under the regional colonial government of Guatemala. Chiapas, Soconusco and Tuxla regions were united to the first time as an intendencia during the Bourbon Reforms in 1790 as an administrative region under the name of Chiapas. However, within this intendencia, the division between Chiapas and Soconusco regions would remain strong and have consequences at the end of the colonial period.

Era of Independence From the colonial period Chiapas was relatively isolated from the colonial authorities in Mexico City and regional authorities in Guatemala. One reason for this was the rugged terrain. Another was that much of Chiapas was not attractive to the Spanish. It lacked mineral wealth, large areas of arable land, and easy access to markets. This isolation spared it from battles related to Independence. José María Morelos y Pavón did enter the city of Tonalá but incurred no resistance. The only other insurgent activity was the publication of a newspaper called El Pararrayos by Matías de Córdova in San Cristóbal de las Casas.Jiménez González, p. 31.

Following the end of Spanish rule in New Spain, it was unclear what new political arrangements would emerge. The isolation of Chiapas from centers of power, along with the strong internal divisions in the intendencia caused a political crisis after the royal government collapsed in Mexico City in 1821, ending the Mexican War of Independence. During this war, a group of influential Chiapas merchants and ranchers sought the establishment of the Free State of Chiapas. This group became known as the La Familia Chiapaneca. However, this alliance did not last with the lowlands preferring inclusion among the new republics of Central America and the highlands annexation to Mexico.Higgens, p. 81. In 1821, a number of cities in Chiapas, starting in Comitán, declared the state's separation from the Spanish empire. In 1823, Guatemala became part of the United Provinces of Central America, which united to form a federal republic that would last from 1823 to 1839. With the exception of the pro-Mexican Ciudad Real (San Cristóbal) and some others, many Chiapanecan towns and villages favored a Chiapas independent of Mexico and some favored unification with Guatemala.