In a twenty year period, roughly a generation, three major events happened that set to course of modern Europe. First was the removal of the Moors from Spain in 1491-1492. Second was the return of Christopher Columbus and the opening of the New World. Third was the Protestant Reformation. Not since the fall of the Western Roman Empire 500 years previous had there been such a base change in the European landscape.

The Theses are written as propositions to be argued in a formal academic disputation, though there is no evidence that such an event ever took place. In the heading of the Theses, Luther invited interested scholars from other cities to participate. Holding such a debate was a privilege Luther held as a doctor, and it was not an unusual form of academic inquiry. Luther prepared twenty sets of theses for disputation at Wittenberg between 1516 and 1521. Andreas Karlstadt had written a set of such theses in April 1517, and these were more radical in theological terms than Luther's. He posted them on the door of All Saints' Church, as Luther was alleged to have done with the Ninety-five Theses. Karlstadt posted his theses at a time when the relics of the church were placed on display, and this may have been considered a provocative gesture. Similarly, Luther posted the Ninety-five Theses on the eve of All Saints' Day, the most important day of the year for the display of relics at All Saints' Church.

Luther's theses were intended to begin a debate among academics, not a popular revolution, but there are indications that he saw his action as prophetic and significant. Around this time, he began using the name "Luther" and sometimes "Eleutherius", Greek for "free", rather than "Luder". This seems to refer to his being free from the scholastic theology which he had argued against earlier that year. Luther later claimed not to have desired the Theses to be widely distributed. Elizabeth Eisenstein has argued that his claimed surprise at their success may have involved self-deception and Hans Hillerbrand has claimed that Luther was certainly intending to instigate a large controversy. At times, Luther seems to use the academic nature of the Theses as a cover to allow him to attack established beliefs while being able to deny that he intended to attack church teaching. Since writing a set of theses for a disputation does not necessarily commit the author to those views, Luther could deny that he held the most incendiary ideas in the Theses.