After central Mexico and the Gulf of Mexico coast, Guanajuato was one of the first areas of Mexico colonized by the Spanish, in the 1520s, for its rich silver deposits. Guanajuato's colonial architecture is very well preserved along with over 35 old churches in its capital alone, and is very European in nature.

Today, Guanajuato's mines are still among the richest-producing silver mines in the world (historically one of the largest). The state also produces tin, gold, copper, lead, mercury, and opals. Guanajuato also leads the nation in shoe production and various farm products such as lettuce and potatoes. Main export products: Motor vehicles and autoparts, footwear, leather goods, chemicals, electric machinery and materials, fruits and vegetables.

In addition to the state capital city of Guanajuato, the state includes the cities of San Luis de la Paz, Acámbaro, Celaya, León, Salamanca, Irapuato, San Miguel de Allende, Salvatierra, the first city of Guanajuato, Cortazar, Tarimoro, Panales Jamaica (Cañones), and Dolores Hidalgo, the cradle of Mexican independence.

The first populist uprising in Mexican history resulted in a march from Dolores Hidalgo upon the capital of the state and the subsequent burning of the granary which held all the "gachupines" (approximately 500 men, women and children from Spain or of pure Spanish descent) by peasants of pure Amerindian or mixed (Mestizo) descent who had been put to work in very harsh conditions.