The university was closed in 1797, a week after the cession to the French Republic of the Austrian Netherlands and the principality of Liège (jointly the future Belgium) by the Treaty of Campo Formio.

In the 15th century the civil administration of the town of Leuven, with the support of John IV, Duke of Brabant,[16] a prince of the House of Valois, made a formal request to the Holy See for a university.

The university flourished in the 16th century due to the presence of famous scholars and professors, such as Adriaan Florenszoon Boeyens (Pope Adrian VI), Desiderius Erasmus, Johannes Molanus, Joan Lluís Vives, Andreas Vesalius and Gerardus Mercator.

In 1519, the Faculty of Theology of Leuven, jointly with that of the University of Cologne, became the first institution to condemn a number of statements drawn from Martin Luther's Ninety-five Theses (preceding the papal bull Exsurge Domine by several months).

This fidelity to the spirit of Van Espen remained alive in the University of Louvain until its abolition in 1797, as evidenced by what Charles Lambrechts wrote[31] in 1818, former rector magnificus and successor to the chair of canon law of Van Espen : "The encroachments of the Catholic clergy and their claims were so vexatious that, at a time when their religion was dominant, no other remedy had been found for their abuse of power except the appeals in question.

This is what prompted the famous Van Espen to write, at the age of eighty, his treatise De recursu ad principem, in order to put a barrier against the ever-recurring abuses of clerical jurisdictions; but this virtuous ecclesiastic, who distributed to the poor all the revenues of the chair of canon law which he occupied at the University of Louvain, was soon obliged to have recourse to appeal as an abuse for himself; still, this remedy could not save him entirely from the persecution of intolerant priests.

Loaded with years, glory and infirmities, he was compelled to seek shelter in Holland from their vexations; he soon died in Amsterdam in feelings of piety and resignation, after having employed his life in defending the discipline and customs of the primitive church, of which he was the most zealous supporter".

[37] Wauthier, head of office of the department of Dyle and the ex-Jesuit De la Serna Santander, librarian of the Central School of Brussels, were responsible for the application of this measure.

It is also very likely that on the occasion of the troubles of the wars of this time, many precious works and documents surreptitiously followed an unofficial route, sometimes with the high aim of saving them from disaster,[39] sometimes with the sordid goal of profiting from it.