The history of the Jews in Mexico began in 1519 with the arrival of Conversos, often called Marranos or "Crypto-Jews", referring to those Jews forcibly converted to Catholicism and that then became subject to the Spanish Inquisition.

During the period of the Viceroyalty of New Spain (1521–1821), a number of Jews came to Mexico, especially during the period of the Iberian Union (1580–1640), when Spain and Portugal were ruled by the same monarch. That political circumstance allowed freer movement by Portuguese crypto-Jewish merchants into Spanish America. When the Portuguese regained their independence from Spain in 1640, Portuguese merchants in New Spain were prosecuted by the Mexican Inquisition. When the monopoly of the Roman Catholic Church in Mexico was replaced with religious toleration during the nineteenth-century Liberal reform, Jews could openly immigrate to Mexico. They came from Europe and later from the crumbling Ottoman Empire, including Syria, until the first half of the 20th century.

Today, most Jews in Mexico are descendants of this immigration and still divided by diasporic origin, principally Yiddish-speaking Ashkenazim and Judaeo-Spanish-speaking Sephardim. It is an insular community with its own religious, social, and cultural institutions, mostly in Mexico City, Monterrey and Guadalajara.

Jews and Conversos were part of the conquest and colonization in Mexico, and key participants in the transatlantic and transpacific trade networks, as well as development of domestic trade. Conversos accompanied Hernán Cortés in 1519. These were members of Jewish families which had been forcibly converted to Christianity to avoid expulsion from Spain after the Reconquest of the Iberian Peninsula from the Moors. The reconquest was followed by the Spanish Inquisition, which made the Conversos one of their targets, with accusations of reverting to Judaic practice. During this time, there were two types of Conversos: Crypto-Jews and Jews who fully converted to Catholicism. The Jews who converted were used to report Crypto-Jews to the Catholic Church and consequently, they were awarded with high-power positions within the Catholic Church. Furthermore, during this time, the Catholic Church was in charge of social welfare and was the most powerful entity. Converso migration to the new Spanish colony began in 1530 after most of the violence from the conquest of the Aztec Empire had subsided and the Spanish Inquisition continued. For several decades, the families were able to live peacefully, integrating into Mexico's elite, with some becoming prominent Catholic clergy and some returning to Jewish practice.

David Nathan proposed that the first coins minted in the Western Hemisphere by Spanish Conquistadors in Mexico City feature a Hebrew letter aleph (א), suggesting evidence for a Jewish presence or influence in Mexico in 1536. He notes that nearly all of the dies prepared under the tenure of the first assayer use the purported aleph symbol in place of the Christian cross potent mark, found almost universally on medieval Spanish and Mexican coinage. Nathan goes on to consider possible Jewish family connections to the known early Mexican mint workers.

The persecution of Jews came to New Spain along with the conquistadors. Bernal Díaz del Castillo described in his writings various executions of soldiers during the conquest of Mexico because they were accused of being practicing Jews, including Hernando Alonzo, who built the boats Cortés used to assault Tenochtitlán. However, the Mexican Inquisition was not fully established until 1571, when it became a threat to Converso and Jewish communities with an initial purge of them from 1585 to 1601. In 1606, Mexico received an order by the King of Spain to free Conversos in Inquisition prisons. This relaxing of the Inquisition in Mexico, which was never as severe as in Spain, allowed more to come over in the first half of the 17th century. New Conversos settled in Mexico City, Acapulco, Veracruz and Campeche as they provided the most opportunities for mercantile activity. Some did move to the more-outlying areas, such as Zacatecas, but they still afforded more opportunities than places farther north. There was a second Inquisition persecution of Conversos from 1642 to 1649. Then, the focus shifted to matters such as blasphemy and moral infractions. However, during the entire colonial period, practicing Jews in Spain or elsewhere could not enter Spanish colonial territory.

One notable episode during the colonial period was the establishment of the New Kingdom of León. In 1567 the Carvajal family arrived to New Spain under nobleman Luis de Carvajal. With the exception of him and a cousin, the family was Crypto-Jewish. In 1579, Carvajal was granted land in what is now northeastern Mexico, just north of what was then considered New Spain. The area welcomed both Conversos and practicing Jews, with about 75% of the initial settlers being secretly Jewish. Some theories state that Monterrey developed as a commercial center despite its colonial era remoteness because of Crypto-Jewish influence. However, Luis de Carvajal and members of his family were persecuted in 1589 for practicing Judaism. De Carvajal's nephew, Luis de Carvajal the Younger, kept memoirs detailing his life and persecution; these are now considered to be the earliest writings by a Jew in the Americas. The auto-da-fé of Mariana Carvajal has become part of Mexican art and literature. By 1641, the colony had grown, and some of the settlers would later move to establish new settlements in Coahuila, Texas, and New Santander.

The largest number of prosecutions by the Mexican Inquisition occurred in the wake of the 1640 dissolution of the Iberian Union, when Spain and Portugal had been ruled by the same monarch. Portuguese merchants more easily entered Spanish America, and a complex community of crypto-Jews connected to transatlantic and trans-Pacific trade networks emerged. Evidence from individual cases prosecuted by the Mexican Inquisition indicates that most crypto-Jews in Mexico or their parents had been born in Portugal, primarily from the Portuguese capital, Lisbon, or from Castelo Branco. There were a few very wealthy Portuguese merchants, who were leaders of the community, but most were shopkeepers and craftsmen. A prominent merchant was Simón Váez, whom the Inquisition accused of letting his house serve as a synagogue in the 17th century until the 1642 persecutions began. He had risen from humble circumstances, but he and other wealthy merchants came to socialize with crown officials and play a prominent role among elites. Their wealth was based on asientos (licenses) for the black slave trade in Mexico since Portugal controlled the African coast, where they were sourced. Portuguese merchants also held contracts for tax farming and supplying the Spanish fleet and forts with stores and munitions.