Born at Baflo, in the Dutch province of Groningen, Agricola was originally named Roelof Huusman.

Educated first by the celebrated school of St. Maarten in Groningen, he matriculated at the universities of Erfurt (BA in 1458) and Louvain (MA in 1465), where he won renown for the purity of his Latin and his skill in disputation. He concentrated his studies on Cicero and Quintilian, and during his university years added French and Greek to his ever growing list of languages. At the end of his life, he was to learn Hebrew in order to be able to read the Old Testament and especially the Psalms unadulterated by translation.

In the 1460s, Agricola travelled to Italy, where he associated with humanist masters and statesmen. From 1468 (?) - 1475, he studied civil law at the university of Pavia, and later went to Ferrara (1475 – 1479), where he became the protégé of Prince d'Este of Ferrara, was a pupil of Theodor Gaza and attended lectures by the famous Battista Guarini. He devoted himself wholly to the study of classical texts. He won renown for the elegance of his Latin style and his knowledge of philosophy. Also while in Ferrara he was formally employed as the organist to the ducal chapel, which was one of the most opulent musical establishments in Europe. He held that post until 1479, after which he returned to the North to become secretary to the city of Groningen. Here at the Cistercian Abbey of St Bernard at Aduard near Groningen and at 's-Heerenbergh near Emmerich in the south-east he was at the centre of a group of scholars and humanists with whom he kept a lively correspondence. Among his correspondents are the musician and choirmaster of Antwerp, Jacobus Barbirianus (Barbireau), Alexander Hegius, rector of the Latin school at Deventer (of Erasmian fame), and the humanist scholar and later famed student of Hebrew, Johannes Reuchlin.

In 1470, he taught a deaf child how to communicate orally and in writing. De inventione dialectica documents this pioneering educational effort.

Once in Germany again, he spent time in Dillingen, where he continued to correspond with humanist friends and colleagues throughout Europe, promoting interest in his project to promote the study of classical learning and the studia humanitatis. He remained an independent scholar, unattached to a university or religious establishment - this independence became a hallmark of humanist scholars. It was in Dillingen in 1479 that Agricola completed his De inventione dialectica (On Dialectical Invention), which argued for the precise application of loci in scholarly argumentation.

In 1481, Agricola spent six months in Brussels at the court of archduke Maximilian (later Maximilian I, the Holy Roman Emperor). Friends attempted to dissuade him from accepting the archduke's patronage; they were afraid the archduke's influence would undermine his philosophical ideals. He also declined the offer to become head of a Latin school at Antwerp.

In 1484, Agricola moved to Heidelberg by invitation of Johann von Dalberg, the Bishop of Worms. The two men had met in Pavia, and they became close friends in Heidelberg. The bishop was a generous benefactor of learning. At this time Agricola began studying Hebrew, and he is said to have published an original translation of the Psalms. In 1485, Dalberg was sent as an ambassador to Pope Innocent VIII in Rome. Agricola accompanied him and was struck gravely ill on their journey.

He died shortly after their return to Heidelberg. Ermolao Barbaro composed an epitaph for him.

De inventione dialectica was very influential in creating a proper place for logic in rhetorical studies, and was of great significance in the education of early humanists. It is a highly original, critical, and systematic treatment of all ideas and concepts related to dialectics. "The significance of De inventione dialectica for the history of argumentation is that it assimilated the art of dialectic to that of rhetoric. Argumentation focused not on truth but on what might be said with reason. Accordingly, Agricola focused on the Topics rather than the Analytics of Aristotle and on Cicero, but also on the writings of historians, poets, and orators. Thus, for Agricola, dialectic was an open field; the art of finding 'whatever can be said with any degree of probability on any subject.'" (Hamilton, David. "From Dialectic to Didactic".) Agricola's De formando studio - his long letter on a private educational programme - was printed as a small booklet and thus influenced pedagogical insights of the early sixteenth century.

Erasmus greatly admired Agricola, eulogizing him in "Adagia" and calling him "the first to bring a breath of better literature from Italy." Erasmus claimed him as a father / teacher figure and may have actually met him through his own schoolmaster Alexander Hegius (most probably one of Agricola's students) at Hegius's school in Deventer. This is a demonstration of Agricola's real legacy: his importance should not be measured so much by what he wrote, but rather by his personal influence over others, and his power stimulus - he was truly a great teacher and model humanist. In addition to Hegius, Agricola's students include Conrad Celtis (in Heidelberg). Nevertheless, Erasmus made it his personal mission to ensure that several of Agricola's major works were printed posthumously.

Agricola's 'De inventione dialectica' has a huge impact on Deaf community. He felt that a person who is born deaf can express himself by putting down his thoughts in writing. The book was not published until 100 years later. His statement that deaf people can be taught a language is one of the earliest positive statements about deafness on record.