Early in life he showed that he was a great "book lover" and a very cultured man who took care to preserve manuscripts scattered about various monasteries.

His name appeared in Russian state documents beginning in 1622 during the reign of Patriarch Philaret of Moscow and his son, Emperor Michael I of Russia.

The patriarch, together with Jeftimije, Metropolitan of Niš and Leskovac, also visited Bishop Maxim Predojević of the Eparchy of Marča in Austro-Hungary (today's Croatia).

Very early on he turned for aid to the Tsardom of Russia which had for a while already been a source of literary (service books) and some financial support.

As the head of the Church, he worked earnestly to strengthen the faltering spirit of the nation through the constant celebration of liturgy and intense writing.

In the book, Pajsije himself reveals his larger ambition: "It was my desire to understand and learn this: whence the Serbs originated, and for what purpose".

He also wrote the Service to St. Symon (Stefan the First-Crowned) and his successor, Gavrilo I (1648–1655) who, like Jovan Kantul, would die a martyr's death while in Turkish captivity in Bursa in 1659.

At the time, the curia in Rome had a program of compulsory conversion to Catholicism that would transfer Serbs into Croats by first having them join the Uniate Church, like in Kiev.

By his wise policy and correct relationship towards Serbian cultural inheritance, Patriarch Pajsije succeeded in creating an atmosphere which produced an unexpected enthusiasm for building and decorating temples.

His activities in the Niš region are reflected in the construction and restoration of Serbian churches and monasteries, as well as in the work of producing book, printing and publishing.

In the seventeenth century, Patriarch Pajsije made great efforts to save older manuscripts, which he himself rebound and placed in safer monasteries or returned to their owners.

Western diplomats who traveled to the Southeastern Europe bore witness that the Serbian Patriarchate of Peć was well-organized.

He canonized the last ruler from the Nemanjići dynasty, Emperor Stefan Uroš V. Patriarch Pajsije was forced to visit Constantinople in 1641 to obtain protection from local Turkish governors.