During the turbulent period of the 16th century, Vizsoly was one of several medium-sized rural settlements in the Abaúj region of the Kingdom of Hungary. The Kingdom of Hungary was divided into three parts in this period. The territory in the central part of the country which was occupied by the Ottoman Empire coexisted with the so-called Royal Hungary in the northern and western part of the country and the Ottoman vassal state of the Principality of Transylvania in the east. Over the course of the 16th century, the Ottoman Empire had expanded ever deeper into the central part of the Kingdom of Hungary, and although the border between the Kingdom of Hungary and the Ottoman Empire had been stabilized for some time by the Treaty of Adrianople in 1568, the vast border region was plagued by raids by smaller Ottoman forces, with local inhabitants forced to pay taxes to both sides. After the establishment of the Fiľakovo sanjak or county (the Ottoman administrative unit), the Ottoman territory gradually expanded – reaching as far north as Dobšiná and to central Abaúj and the southern Zemplín region in the northeast and east. During the second half of the 16th century, Vizsoly also fell under the control of the Fiľakovo sanjak.

In these complicated conditions, the ideas of the Reformation also continued to spread across the Kingdom of Hungary. The development of the Reformation was greatly influenced by the Peace of Augsburg in 1555 which ended the period known as the wars of religion. According to the established rule of “cuius regio eius religio” (whose realm, his religion), the monarch’s religion was also transferred to his or her subjects, but this only applied to the Catholic and Lutheran religions and excluded the Calvinist, Zwinglian, Anabaptist or Antitrinitarian movements. Although the religion of the inhabitants of serf towns and villages was essentially dependent upon the religion of their landlords, the constant threat of the Ottoman Empire also allowed other Protestant movements to spread in the Kingdom of Hungary among both the landlords and their subjects. While the Lutheran Reformation had primarily spread among Slovaks and Germans (Lutherans/Evangelicals), the Calvinist Reformation (Calvinists/Reformed Church) began to gain favour among Hungarians. The western parts of the Kingdom of Hungary and several smaller and isolated enclaves remained mainly Catholic.

One of the aims of Protestantism was the effort to spread the word of God and the Bible in national languages. Translations of various sections of the Bible into Hungarian dated back to the Middle Ages and were preserved through several codices and their transcripts from the period of 1493 to 1576 including, among others, the Bratislava or Nové Zámky Codex. Thanks to the spread of the Reformation and typography in the territory of the Kingdom of Hungary, translations of individual smaller sections of the Bible into Hungarian were made from the 1530s onwards, such as the Letters of the Apostle Paul (1533), the Gospels and the New Testament (1536, 1541, 1586), the Psalms of the Old Testament (1548) and parts of the Old Testament (1551-1555, 1567), but these works were translations from the Latin Vulgate Bible or from the Septuagint or Greek Old Testament. In the 1570s, Peter Bornemisza made an unsuccessful attempt to publish a separate Hungarian translation of the entire Bible at Plavecký Castle and Hlohovec in cooperation with Valentin Mančkovič, the printer who would later publish the Vizsoly Bible.

In around 1580 Vizsoly became the Calvinist seat of the landlord Gáspár Mágócsy and his wife Judita Alaghy, two of the most active proponents of the Reformation in the Kingdom of Hungary. In 1586, with the support of Gáspár and András Mágócsy, Gáspár Károlyi began working actively on his translation of the Bible into Hungarian. By this time, Károlyi was already a prominent Calvinist figure, the superintendent of the Košice Valley diocese and a preacher in the nearby town of Gönc. He had been involved in translating of the Bible since the period of his studies in Brașov and Wittenberg, the cradle of the Reformation, and some passages of his translations had been printed in as early as 1563. Preparations for publication were suspended during 1586-1587 when the Mágócsy brothers died fighting the Ottoman forces and Károlyi lost his wife and three daughters in a typhus outbreak. However, activities were resumed in 1587 after Judita Alaghy’s marriage to Sigismund Rákóczi, a successful defender of Hungary against the Turks and the future Prince of Transylvania. Although recent research suggests that Károlyi likely translated the entire New Testament by himself, at least three other clerics participated in the translation of other sections of the text. In addition to the afore-mentioned Latin Vulgate Bible and Septuagint, the then famous Hebrew and Greek parts of biblical texts also became the basis for the translation in addition to some biblical translations and commentaries by famous 16th century Bible scholars, such as Franciscus Vatablus, Sebastian Münster, Santes Pagninus and Immanuel Tremellius, and earlier Hungarian translators such as Gáspár Heltai, Péter Méliusz Juhász and István Székely. The translation of the Bible was most likely completed only after its printing began.