Pakke Tiger Reserve lies in the undulating and hilly foothills of the Eastern Himalayas in Arunachal Pradesh's Pakke Kessang District at elevations ranging from 150 to 2,000 m (490 to 6,560 ft). It is bounded by Bhareli or Kameng River in the west and north, and by Pakke River in the east. It is surrounded by contiguous forests on most sides.To the east lies Papum Reserve Forest with an area of 1,064 km2 (411 sq mi). Towards the south and south-east, the sanctuary adjoins reserve forests and Assam's Nameri National Park.
To the west, it is bounded by Doimara Reserve Forest with an area of 216 km2 (83 sq mi) and Eaglenest Wildlife Sanctuary; and to the north by Shergaon Forest Division. Selective logging on a commercial scale occurred in the reserve forests until 1996.
The main perennial streams in the area are the Nameri, Khari and Upper Dikorai. West of Kameng River are Sessa Orchid Sanctuary and Eaglenest Wildlife Sanctuary.