Mesoamerica is a historical region and cultural area that begins in the southern part of North America and extends to most of Central America, thus comprising the lands of central Mexico, Belize, and Guatemala, El Salvador, Honduras, and Nicaragua, and northern Costa Rica. In the pre-Columbian era many societies flourished in Mesoamerica for more than 3,000 years before the Spanish colonization of the Americas, begun at Hispaniola island in 1493. In world history, Mesoamerica was the site of two historical transformations: (i) primary urban generation, and (ii) the formation of New World cultures from the mixtures of the indigenous Mesoamerican peoples with the European, African, and Asian peoples who were introduced by the Spanish colonization of the Americas.

In the 16th century, Eurasian diseases such as smallpox and measles, which were endemic among the colonists but new to North America, caused the deaths of upwards of 90% of the indigenous people, resulting in great losses to their societies and cultures. Mesoamerica is one of the five areas in the world where ancient civilization arose independently (see cradle of civilization), and the second in the Americas. Norte Chico (Caral-Supe) in present-day Peru, arose as an independent civilization in the northern coastal region.

As a cultural area, Mesoamerica is defined by a mosaic of cultural traits developed and shared by its indigenous cultures. Beginning as early as 7000 BCE, the domestication of cacao, maize, beans, tomato, avocado, vanilla, squash and chili, as well as the turkey and dog, resulted in a transition from paleo-Indian hunter-gatherer tribal groupings to the organization of sedentary agricultural villages. In the subsequent Formative period, agriculture and cultural traits such as a complex mythological and religious tradition, a vigesimal numeric system, a complex calendric system, a tradition of ball playing, and a distinct architectural style, were diffused through the area. Also in this period, villages began to become socially stratified and develop into chiefdoms. Large ceremonial centers were built, interconnected by a network of trade routes for the exchange of luxury goods, such as obsidian, jade, cacao, cinnabar, Spondylus shells, hematite, and ceramics. While Mesoamerican civilization knew of the wheel and basic metallurgy, neither of these became technologically relevant.

Among the earliest complex civilizations was the Olmec culture, which inhabited the Gulf Coast of Mexico and extended inland and southwards across the Isthmus of Tehuantepec. Frequent contact and cultural interchange between the early Olmec and other cultures in Chiapas, Oaxaca and Guatemala laid the basis for the Mesoamerican cultural area. All this was facilitated by considerable regional communications in ancient Mesoamerica, especially along the Pacific coast.

During this formative period distinct religious and symbolic traditions spread, as well as the development of artistic and architectural complexes. In the subsequent Preclassic period, complex urban polities began to develop among the Maya, with the rise of centers such as Aguada fénix and Calakmul in Mexico; El Mirador, and Tikal in Guatemala, and the Zapotec at Monte Albán. During this period, the first true Mesoamerican writing systems were developed in the Epi-Olmec and the Zapotec cultures. The Mesoamerican writing tradition reached its height in the Classic Maya logosyllabic script.

Mesoamerica is one of only six regions of the world where writing is known to have independently developed (the others being ancient Egypt, Peru, India, Sumer, and China). In Central Mexico, the city of Teotihuacan ascended at the height of the Classic period; it formed a military and commercial empire whose political influence stretched south into the Maya area and northward. Upon the collapse of Teotihuacán around 600 AD, competition between several important political centers in central Mexico, such as Xochicalco and Cholula, ensued. At this time during the Epi-Classic period, the Nahua peoples began moving south into Mesoamerica from the North, and became politically and culturally dominant in central Mexico, as they displaced speakers of Oto-Manguean languages.

During the early post-Classic period, Central Mexico was dominated by the Toltec culture, and Oaxaca by the Mixtec. The lowland Maya area had important centers at Chichén Itzá and Mayapán. Towards the end of the post-Classic period, the Aztecs of Central Mexico built a tributary empire covering most of central Mesoamerica.

The distinct Mesoamerican cultural tradition ended with the Spanish conquest in the 16th century. Over the next centuries, Mesoamerican indigenous cultures were gradually subjected to Spanish colonial rule. Aspects of the Mesoamerican cultural heritage still survive among the indigenous peoples who inhabit Mesoamerica. Many continue to speak their ancestral languages, and maintain many practices harking back to their Mesoamerican roots.