The Complutensian Polyglot Bible is the name given to the first printed polyglot of the entire Bible. The edition was initiated and financed by Cardinal Francisco Jiménez de Cisneros (1436–1517) and published by Complutense University in Alcalá de Henares, Spain. It includes the first printed editions of the Greek New Testament, the complete Septuagint, and the Targum Onkelos, a translation of the Torah. Of the 600 six-volume sets which were printed, only 123 are known to have survived to date.

The polyglot Bible was the result of Spain's long-lasting tradition of translations of texts. Through centuries the intellectual class of the Iberian peninsula had developed a deep understanding of the issues of translation and the difficulty of conveying, or even interpreting meaning correctly across languages. Religious texts were known to be particularly difficult due to their high metaphorical content and how dependent on the context in which they were written they tended to be. This sparked a debate in Spain about the convenience of continuing the translation of religious texts, and the best way to do it, over a century prior to the Reformation.

The customary answer to this debate was to ask religious authorities to examine the translation and cross-check and compare different translations with contemporary Castilian, but that in turn created a debate about the qualifications of the religious authority itself to properly translate from the original sources. One of the answers to this debate was the polyglot Bible, which Cisneros hoped would end the issue forever.

Diego López de Zúñiga was the chief editor, and was fluent in Latin as well as both Aramaic and Arabic. He was given a team of various translators. Converted translators and academics were favoured and specifically sought since they were fluent in the source languages and the cultures of the texts. Second in command, Alfonso de Zamora (1476–1544) was a converted Jewish scholar, an expert in Talmudic studies, and spoke Hebrew as his first language. Other conversos working on the project were Alfonso de Alcalá and Pablo de Coronel. Demetrius Ducas (a scholar from Crete), Hernán Núñez de Toledo ("The Pincian") and Juan de Vergara were in charge of the translation from Greek manuscripts. Antonio de Nebrija was specifically called for the translation of the Latin Vulgate. Hernán Núñez de Toledo was also the chief Latinist. The scholars met in Alcalá de Henares, a city near Madrid also known by its Latin name Complutum, at Complutense University.

The New Testament was completed and printed in 1514, but its publication was delayed while work on the Old Testament continued, so they could be published together as a complete work.

The Complutensian Old Testament was completed in 1517. Cardinal Cisneros died in July 1517, five months after the Polyglot's completion, and never saw its publication. Further delays happened when, following the death of Cardinal Cisneros, the text was confiscated by the Holy Roman Emperor Charles V.

Erasmus's four-year exclusive privilege in 1516 (and the papal privilege given to the First Biblia Rabbinica in 1518) may have also been a delaying factor: Pope Leo X finally sanctioned it in 1520, at which time the civil war in Castile, the Revolt of the Comuneros, broke out, causing delays.

The immediate direct influence of the Complutensian Polyglot was attenuated because, according to a much later letter of King Philip II of Spain, a significant number of copies were lost in a shipwreck in transit to Italy around 1521.