In 1837, the "Exhibition of Works from the Province" was established in Arkhangelsk, initially consisting of 94 items of natural history and ethnographic significance. The collections were stored and expanded in a separate room at the Public Charity Office, and in 1840 they were moved to the official residence of the civil governor.

For many decades, representatives from various social strata contributed to the museum's collections: governors, officials, intellectuals, merchants, and peasants.

With the advent of Soviet power, a decision was made to create the Northern Regional Museum based on the Arkhangelsk City Public Museum, the Diocesan Antiquities Repository at the Arkhangelsk Church Archaeological Committee, the Fisheries Museum of the Far North, and the museum of the Arkhangelsk Society for the Study of the Russian North.

During the Great Patriotic War, the museum continued its activities, enriching its collections, including military themes. Staff conducted educational work both in the museum and in military hospitals in Arkhangelsk. In 1942, the museum building was damaged twice by Nazi air raids. That same year, the main collections were evacuated to Solvychegodsk for their preservation and returned safely in 1944.

In the late 1950s and early 1960s, systematic studies of the region began through annual historical, archaeological, and natural science expeditions. As a result of this work, collections of prehistoric and medieval archaeology, folk clothing, handicrafts and trades, household items and tools, technical monuments, and natural science were significantly expanded and reformed. In the 1970s and 1980s, the museum's funds were enriched with a diverse collection of materials on urban culture and everyday life.

Today, the museum's collection numbers nearly 300,000 items and is the largest comprehensive collection in the region, making up half of the museum fund of the Arkhangelsk region.

The Arkhangelsk Regional Museum actively participates in international cultural events and exhibition exchanges with Russian and foreign museums, maintains close ties with neighboring regions of Russia and international contacts, especially with colleagues from Scandinavian countries, primarily Norway. This cooperation led to the creation of the Barents Region Museum Network. In 2018, the museum became one of the organizers and venues for the IX Russian-Norwegian Cultural Forum.

Traditional forms of museum work are successfully combined with modern multimedia technologies and interactive exhibition spaces.