The collection of manuscripts of the Jagiellonian Library grew together with the university. The most important part of the collection is composed of scientific treatises documenting research and didactic work of the Jagiellonian University from its early days. They include textbooks, professors' lectures, students' notes from lectures, and finally professors' libraries bequeathed to the university library. Apart from works related to the teaching activities of the university, they include scientific treatises representing all four faculties of the university of the 15th century, which were created in Cracow or brought over here from other centres of academic studies. Their content show the important role that the Cracow school played in the development of sciences in the late Middle Ages and the Renaissance.

They document intellectual achievements as well as the contribution of Cracow scholars to the culture of Europe at the time.

The works, which are of special importance, include: Commentariolum, super ťTheoricas novas Ť Georgii Peurbachii in Studio generali Cracoviensi … corrogatum. The masterpiece of Wojciech of Brudzewo (died ca. 1495) in which he questioned the widely accepted theories of eccentrics, epicycles and equants. Even though the author was still an advocate of the geocentric theory, his views constitute a step on the way to create the heliocentric image of the world. The manuscript is a copy from 1493, accession MS BJ 2703.

There were at least three scientists in the late 15th century who together with the father of Polish cartography Bernard Wapowski, carried out geographical studies. They included: Piotr Gaszowiec from Łoźmierza Polska (ca. 1430-1474), who carried out astronomical observations and calculated longitude; Jan of Głogów(ca. 1445-1507), who in his personal copy of Ptolemy's Almagest left a small geographical treatise with distances, longitude and latitude, and geographical co-ordinates of Cracow etc.; and Maciej of Miechów (1457-1523), a doctor, geographer and a historian who most likely made Wapowski familiar with the issues concerning the geography of Sarmatia.

Bernard Wapowski, (ca. 1450 or 1470-1535) a Cracow canon, historiographer and the secretary of King Sigismund I the Old, was by far the most outstanding Polish cartographer of the 16th century. In 1506 in Rome together with Marco of Benevent, Wapowski worked to update the map by Nicholas of Cusa from 1491.

In 1507 he also worked on an update of the map of middle Europe of Claudius Ptolemy's Geography. He is credited with adding 100 names of towns to the new edition of the map.

Many manuscripts of the Jagiellonian Library represent medical sciences. Of great popularity was a medical text-book written by Tomasz of Wrocław, Bishop of Sarepta. His books found their place in the university library together with books by Maciej of Miechów, Andrzej Grzymała of Poznań, or the Italian John of Pavia, the rector of the Cracow University and the Dean of the Faculty of Medicine in 1432 and 1433.

Among many famous names of special importance Jan Elgot was a prominent stylist. The most famous lawyers of the 15th century were Stanisław of Skarbimierz and Paweł Włodkowic. Stanisław (1360-1431), a lawyer, philosopher, and theoretician of international law, a professor and the first rector in 1400, created the first system of war law formulated in De bellis iustis and De rapina. He became the precursor of the international law of nations as he created the first juridical definition and justification of the just war.

During the difficult period of the schism dating back to the election of the Avignon Pope in 1378 counciliaristic tendencies began to emerge to bring back unity within the Church. At the Councils of Basel and Constance the Polish delegation played an important role as supporters of counciliarism. In Basel two treatises on the superiority of the Council over the Pope written by Tomasz of Strzępino (1398-1460) and Benedykt Hesse of Cracow (d. 1456) were read. Other treatises on the same subject were written by Jan Elgot, Jakub of Paradyż, Benedykt Hesse and Wawrzyniec of Racibórz. Speeches delivered by the Polish university delegation are in MS BJ 1217 from 1420-1441.