Beginning the 10th century, the territory of the current Minsk region was part of Kievan Rus', the Principality of Polotsk, and later it was included in the Grand Duchy of Lithuania.

During the collapse of the Russian Empire due to the Civil War, the western part was annexed to Poland in 1921, while the east became Soviet Belarus.

The Polish National District with its capital in Dzyarzhynsk was located in the Soviet-controlled part of the current oblast in the interwar period.

The Minsk region was established on 15 January 1938, based on the amendment of the Constitutional Law of the USSR.

On 20 September 1944, by the decree of the Presidium of the Supreme Soviet of the USSR, the Gressky, Kopyl, Krasnoslobodski, Luban, Slutsky, Starobin, Starodorozhski districts and the city of Sluck were removed from the Minsk region and transferred to the newly formed Bobruisk region.