It was founded by King of Bohemia and Holy Roman Emperor Charles IV, who established it by Golden Bull in 1348. It was confirmed by pope Clement VI as a studium generale on request by the emperor. Based on the model of Bologna and Paris the university was opened in 1349 and sanctioned by emperor Charles IV in 1349. Archbishop Arnost of Pardubice took an active part in the foundation by obliging the clergy to contribute. The lectures were held in the colleges, of which the oldest was named the Carolinum. The university was sectioned into Czech, Bavarian, Saxon and Polish parts called nations.
In 1403 the university forbade its members to follow the teachings of Wycliff, but his doctrine continued to gain in popularity. Jan Hus had translated Wycliff's Trialogus into the Czech language. He was dean and rector of the university. The other sections (called nations) of the university declared their support for the side of pope Gregory XII. Hus knew how to make use of king Wenceslaus' opposition to Gregory. By the decree of Kutna Hora (Dekret Kutnohorský in Czech) in 1409, Hus and the Czech nation had three votes in all affairs of the university, while only one vote was for all the other nations combined. The result of this was the emigration of the German professors and students to the University of Leipzig[?] in May 1409. The Prague university lost its largest part of the students and the faculty. From then on the university declined to a national institution with a very low status. For decades no degrees were given and only the faculty of arts remained. Emperor Sigismund, son of Charles IV, took what was left into his personal property and some progress was made,and again later under emperor Rudolph II, when he took up residence in Prague. The emperor Ferdinand I had called the Jesuits to Prague and they had opened an academy. Soon they took over, were expelled 1618-21, but by 1622 they had a predominant influence over the emperor. An Imperial decree gave the Jesuits supreme control over the entire school system of Bohemia, Moravia and Silesia. The last four professors at the Carolina now resigned and all of the Carolina and nine colleges went to the Jesuits. The right of handing out degrees, of holding chancellorships and of appointing the secular professors was also granted to the Jesuits.
Cardinal Ernst, Count von Harrach actively opposed this union of power and prevented the drawing up of the Golden Bull for the confirmation of this grant. Cardinal Ernst funded the Collegium Adalbertinum and in 1638 emperor Ferdinand III limited the teaching monopoly enjoyed by the Jesuits.He took from them the rights, properties and archives of the Carolinum etc. and made the university once more independent under an imperial protector.During the last years of the Thirty Years' War the Charles Bridge in Prague was courageously defended by students of the Carolina and Clementina.
The dilapidated Carolinum was rebuilt in 1718 at the expense of the state. Since 1650 those who received any degrees took an oath to maintain the Immaculate Conception of the Blessed Virgin, renewed annually. The rebuilding and the bureaucratic reforms of universities of Austria in 1752 and 1754 deprived the university of many of its former privileges.
For the first time Protestants were allowed and soon after Jews. The university funded an additional Czech professorship. By 1863 out of 187 lecture courses 22 were held in Czech language. The Czechs were not satisfied. Consequently after long negotiations the Carolo-Ferdinandea was divided into a German and a Czech Karl-Ferdinand University by law of 1882. Each section was entirely independent of the other, only the aula and the library were used in common. While the inhabitants of Prague had remained roughly even, by 1909 the Czech students at the Czech Karl-Ferdinand University numbered 4300 students and the students at the German Karl-Ferdinand University numbered 1800.