The northeastern corner of the reserve is the locations of Ooldea, and central north Cook on the railway line, and the northern boundary is adjacent to the Maralinga Tjarutja Aboriginal lands.
The northern boundary has the abandoned railway locations of Hughes, Denman, Fisher, O'Malley and Watson, as well as being the section of line that is the known as the longest railway straight.
Nullarbor National Park and Nullarbor Regional Reserve protect the world's largest semi-arid cave landscape, which is associated with many Aboriginal cultural sites. Wildlife inhabiting in the park includes the Southern Hairy-nosed Wombat