The idea of the creation of a nature reserve in the upper Pechora, as a sable zakaznik (sanctuary), was proposed in 1915 by S. T. Nat, the Chief Forester of Vologda Guberniya, in his article in Lesnoy Zhurnal (Forest Journal). The nature reserve was created on May 4, 1930, originally occupying 11,350 square kilometers. The borders of the reserve were set on July 30, 1931.

Originally, the reserve's main office was built in the village of Ust-Ilych, at the fall of the Ilych into the Pechora. Access to that location being extremely difficult, the main office was moved in 1935 to the village of Yaksha, further upstream on the Pechora, but closer to the Kama River basin, via which the area communicated with the outside world in those days.

In 1951 the reserve was greatly reduced in size, to a mere 930 km2; its area became non-contiguous, with a small lowland section near Yaksha being separated from the highland part. In 1959 the area of the reserve was increased to its current size (7,213 km2), but it still remains non-contiguous. To better protect the reserve, in 1973 a buffer area of 324 km2 (similar in status to a national forest in the United States) was created outside of the reserve; the size of the buffer area size was increased in 1984 by additional 330 km2.

Since 1986 reserve has been listed by UNESCO as one of the biosphere reserves of the World Network of Biosphere Reserves. In 1995 the forest area including the Pechora-Ilych Nature Reserve and its northern neighbor, the Yugyd Va National Park, were recognized by UNESCO as a World Heritage Site, under the name Virgin Komi Forests.