Human settlements in the area have been dated to between 6,000 and 4,000 years ago, in the southern part of the region, with the earliest found in the far south of the area in what is now the municipality of
Cadereyta de Montes, in an area called the Mesa de León.
 The earliest inhabitants were hunter-gatherers; however over time, many developed sedentary agricultural villages by the end of the
Pre Classic period .
 The development of these villages was bolstered by migration of agricultural peoples from the
Mexican Plateau and the
Gulf of Mexico coast, especially from the latter.
 Agriculture was concentrated in the lower valley areas, the few plains and some sides of mountains. This also included the cutting of forests to make more agricultural land. Most settlements are found near springs, ponds and small lakes as they were the most readily usable sources of water, instead of the rivers which ran deep inside narrow canyons.
 This included the Huastecas, who were found mostly in the far northeast of the region, noted for growing cotton.
The height of settlement of the area came between the 6th and 10th centuries, with the largest number of successful human settlements, with an economy based on farming and mining.
 During this time, the area saw intense commercial traffic and cultural exchanges between
Gulf of Mexico, the
Huasteca area and the
Mexican Plateau, with artifacts related to Río Verde in San Luis Potosí, Teotihuacan, Tula, west to the Bajío and from the valleys of Querétaro and San Juan del Río all found.
 However, the peoples of the Sierra Gorda had more ties with peoples to the west, north and east, than with the
Mexican Plateau to the south.
 This is when the cities of
Las Ranas and
Toluquilla grew. The two cities’ economies were based on the control of trade routes and mining of
cinnabar, used as a red
pigment. The mining of cinnabar required coordinated and hierarchical labor practices for the various tasks involved, which would lead to the development of these cities. This area was the primary provider of red pigment to
Between 200 and 1000 CE, the area was culturally divided into three regions, Río Verde, the Serrana Cultura and the Huasteca.
 The Río Verde region is located in the northwest of the state of Querétaro into San Luis Potosí. The Serrana Culture is found around the archeological sites of Las Ranas and Toluquilla, which dominated most of the trade routes, and had the greatest population during the
Classic Period (200-900CE). The Huasteca region is in the far northeast with major settlements at Tancoyol, La Campana, Tancama and Tonatico, which had fertile lands. The Otomi arrived in the area in 800 CE and settled peacefully.
The development of cities and dominions came to a halt in the 11th century, after being in decline for over 300 years before that. During the
Post classic (900–1521) all of the area's cities in Querétaro would become abandoned. There are two theories as to why this occurred. The first is that there was climate change during this time, which caused the area to dry out. The second was that it was due to social phenomena, as a number of cities in Mesoamerica, including
Teotihuacan went into decline. Eventually the cities of the Sierra Gorda were abandoned altogether, but this may have been gradual. Evidence at Las Ranas and Toluquilla indicate a non violent transition, as farming communities were abandoned and replaced by hunter-gatherer communities.
The hunter gatherer cultures that moved in from the 11th century remained until the colonial period, and were categorized together as "
Chichimecas". These consisted in various ethnicities including
Jonaz. All speak languages in the
Oto-Manguean family, with differences mostly cultural. The Pames were found mostly in the east with the Jonaz in the west. In addition, there were also groups of Otomis and Huasteca to be found.
The areas in the far east and far west of the Sierra Gorda were dominated by the Spanish soon after the
Spanish conquest of the Aztec Empire. What is now the Sierra Gorda in Guanajuato and Hidalgo states had Spanish cities in them by the middle of the 16th century. The main reason for this was that these areas had higher concentrations of mineral deposits. Another factor was that the indigenous peoples in these areas were relatively compliant to Spanish rule, especially in Hidalgo, where the Otomi had already been dominated by
The Spanish entered the heart of the Sierra Gorda early, with
Nuño de Guzmán conquering the Oxitipa dominion, which encompassed
Xilitla, Tancoyol and Tilaco in 1527.
 However, during the early colonial period, the Querétaro Sierra Gorda would remain dangerous territory as the Chichimecas fought Spanish domination.
 with the first war between the Chichimeca Jonaz and the Spanish occurring in 1554.
 During the 16th and 17th century, the Spanish would surround this area on west, east and south, with military and missionary incursions into the interior. Spanish settlements were begun to the south of it, such as the Villa de Cadereyta in order to form a bulwark against the nomadic Chichimeca tribes. In the late 16th century, a number of forts were established in the area including El Jofre and Jalpan.
 The incursions were provoked not because of significant mineral deposits in northern Querétaro, but rather, the area laid on roads which led into mining areas such as
Missionary work began in 1550 with an
Augustinian mission in Xilitla, San Luis Potosí. However, like military incursions, evangelism would occur from outside the heart of the region and gradually move inwards with many failures.
 However, the challenge to the Spanish was not only the hostility of the native peoples, but also this area lacked cities or towns, or the social hierarchy that was taken advantage of in other areas of
Mesoamerica. In this region, the Spanish would have to create population centers.
Systematic evangelization of the Querétaro area would not be attempted until the 17th century, when Augustinians in the east and
Franciscans in the west began building missions in 1670 and 1680s, under the military protection of Captain
Jerónimo de Labra. However, Labra died in 1683, and the missions were unprotected. The
Dominicans would arrive soon after but by 1700, both they and the Augustinians and Dominicans abandoned missions in most of the area, leaving only the Franciscans in
Tolimán, Cadereyta, Escanela and Maconí.
 Many of the missions built in the interior during the 16th and 17th centuries were destroyed shortly after they were built.
 Successful missions were established in the far south of the region, with the mission of San Francisco Tolimán in 1683,the mission of San José de Vizarrón in the 1740s.
 Because of this, much of the first evangelization efforts undertaken before the mid 18th century have been largely forgotten.
In 1740, the colonial government in
Mexico City decided to extinguish indigenous resistance the Sierra Gorda, and send an expedition headed by
José de Escandón to accomplish this. Escandón mostly fought the Chichimeca Jonaz, culminating in the
Battle of Media Luna in 1749, when the Chichimeca were decisively defeated.
 Legend states that at the end of the battle, the Chichimecas and Ximpeces climbed the hill the battle was fought on to commit collective suicide rather than to be integrated into the Spanish order.
In the far north of Querétaro, the Pames were more pacifistic and accepting of Spanish domination. It was these people who the Franciscans were able to group into larger settlements around missions.
 Although the mission in Jalpan was established before
Junípero Serra's 1750 arrival into the region, Serra is given credit for building the five main missions of this area and completing the evangelization of the local people.
 In reality, the missions were built by Pame hands, under the direction of various Franciscan monks including José Antonio de Murguía in Concá, Juan Crispi in Tilaco, Juan Ramos de Lora in Tancoyol and Miguel de la Campa in Landa.
 However, the vision for the building of the missions was Serra's, as he imagined a type of
utopia based on Franciscan principles. Serra insisted that the missionaries learn the local languages and experience hunger along with the rest of the population. There was still hostility to the Spanish presence, and Serra's response was economic as well as spiritual.
 The portals of the five main mission churches reflect this vision as well. The style of the five missions is called "Mestizo Baroque" as the indigenous elements are more clearly visible here than in other Baroque structures further south. The Baroque is mostly confined to the portals of the main facades and are meant to function much as an altarpiece, and to teach a world view to the natives of the area.
 Serra spent eleven years in the Sierra Gorda before moving on in the late 1760s.
 The missions established in Querétaro would be the first of a long series of missions that would be established as the Spanish made their way north into what is now southern California.
Various uprisings occurred in the area in 1810 as part of the
Mexican War of Independence. The town of Jalpan was burned and sacked by royalist forces in 1819.
In the 19th century, the area was still heavily dominated by indigenous people, with small settlements of
criollos. Conflicts between the indigenous groups and others began at this time over natural resources such as land, water and especially forests. The
Sierra Gorda Rebellion began in 1847 by deserters from the Mexican army. The uprising spread to nearly all parts of the Sierra Gorda region from Guanajuato to San Luis Potosí to
Veracruz, with the most activity in Santa María del Río,
Xichú and Rioverde between 1847 and 1849. The rebels demanded free use of various lands, the abolition of levies, the division of haciendas and the termination of parish church rights to land. Initial efforts by authorities to subdue the uprising were only partially successful. Rebels had control of various cities such as
Ciudad Fernández, Rioverde and
Santa María del Río by 1849. However, the government caught the most important rebel leader by the name of Quiroz that same year and executed him. This broke the main resistance and the government was able to put much of the rebellion down by 1850.
From Jalpan, General
Tomás Mejía led military actions here against the Liberal government installed in the state of Querétaro and the country. He managed to take the main square of
Querétaro in 1857. However, at the end of the
Reform War, he was executed along with
Maximilian I of Mexico .
In 1880, the first major (dirt) road was built through the area to connect it with the capital. This spurred economic development in the region.
Jalpan gained city status in 1904 as it already has electricity, telephone, telegraph and a sugar cane mill.(arqueomex) In 1911, the Grupo Revolucionario Aquiles Serdán was created in Jalpan under Policarpo Olvera and fought with the forces under
Francisco I. Madero .
The modern Querétaro-Jalpan highway was built between 1962 and 1970, along with a number of other roads, bridges, electrification and water services.
The economy of the region had remained mostly the same since the colonial period, mostly based on agriculture and livestock.In 1989, this began to change as local residents formed the non governmental organization Grupo Ecológico Sierra Gorda. The group works with environmental education, reforestation and waste management among other things. The group worked to get the biosphere declared in 1997 and has had international support since then. This has spurred ecotourism.
The mission churches of the area suffered damage from the
Mexican War of Independence and the
Mexican Revolution, and had been all but completely abandoned by the second half of the 20th century. In the 1980s, the churches were "discovered" by a group from
INAH from Xilitla. The churches were restored in the 1980s and 1990s, and declared a World Heritage Site in 2003.
Cinnabar and mercury mining has been part of the southern Sierra Gorda since the Pre classic period. This mining remained important until the 1970s, when most of the commercial mines closing and the last, in Maconí, closed in 2000. However, there are still at least six families known to mine the element on a very small scale. According to researchers, the long history of mercury mining here has caused the contamination of the environment as it built up over time. They believe this is behind the high levels of certain chronic diseases in the region.
 There are plans to build a dam on the Extóraz River, 85 meters tall to store 118 million m3 of water. The water would be transported by aqueduct 138 km to the city of Querétaro. However, there is local opposition to the project.