It is located in the southwestern part of Belarus, bordering the Podlasie and Lublin voivodships of Poland on the west, the Volyn Oblast and Rivne Oblast of Ukraine on the south, the Grodno Region and Minsk Region on the north, and Gomel Region on the east. The region covers at total area of 32,800 km², about 15,7% of the national total.
Kametnets District of Brest Region in few kilometers to the South-West from Vysokaye town on the Bug River the western extreme point of Belarus is situated. 2,7% of the territory are covered with Belovezhskaya Pushcha National Park, 9,8% are covered with 17 wildlife preserves of national importance.
It is often dubbed the Western gateway to Belarus. Geographically, the Brest Region belongs to the area known as Polesia. The area of the region was part of the Second Polish Republic from 1921 until 1939 largely as the Polesie Voivodeship, when it was joined to the Byelorussian Soviet Socialist Republic. Northeastern part of it was administrated as part of Nowogrodek Voivodeship.