Desiderius Erasmus wrote On the Freedom of the Will at the request of his countryman Pope Adrian VI, who desired some form of resolution to the fundamental disagreements that had plagued the church ever since Luther had nailed his ninety-five complaints to the church door in Wittenberg in 1517. Unsurprisingly, the essay therefore has a reconciliatory tone—with none of the venom that was characteristic of Erasmus’s later responses to Luther—and even has occasional affirmations delivered by the Dutchman on certain Lutheran doctrines.

The principle disagreement Erasmus has with Luther concerns the efficacy of human free will: whether people can actively make decisions or whether such decisions are predestined (as Luther had asserted), with virtuous actions only being possible by means of divine grace. Erasmus does not champion the orthodox Catholic position that Luther opposed—namely that humans were at liberty to decide, even in the smallest of life’s choices, the path of good or of evil.

Erasmus’s tripartite understanding of human action includes the idea that knowing what is good and performing what is good is only achievable through grace. However, willing what is good comes down to human merit. By this means, Erasmus argues, one can recognize the importance of one’s total surrender to God—one of the Lutheran doctrines of which Erasmus approved—while also allowing for some degree of human responsibility. This human involvement was considered vital in society to Erasmus; he believed that a lack of responsibility would lead to a breakdown in moral order.

Erasmus was also able to agree with Luther on the supremacy of the Bible in informing Christian teachings, but he did contest Luther’s radical humanist assertion that one's own mind was a better instructor on scriptures than the collected writings of all former Catholic theologians. In doing this, he appeals to the virtue of humility that lies at the center of Christian teaching, asserting that no one individual could possibly hold a perfect understanding of God’s will. He states that even if they should never be considered equivalent with the Bible, the work of theologians provides valuable insights that could inform individual interpretations of scripture.

Erasmus’s attempts to reconcile the two divergent groups within Christendom failed: the conflict between these groups continued to escalate over the subsequent decades and centuries. His essay also received a scathing response from Luther, who did not share Erasmus’s belief that mild and tolerant debate should prevail in scholarly discourse.

However, On the Freedom of the Will undoubtedly influenced thinkers of later centuries, both Catholic and Protestant. The balance that Erasmus sought concerning the nature of free will was appealing to those who saw the notion of "double predestination" (as championed in later centuries by Calvinists) as unreasonable, and it was also appealing to those who thought that radical humanist movements afforded too little influence to divine intervention.