[1] The R81 starts at a junction with the R71 road in Polokwane (capital of the Limpopo Province), in the suburb of Fauna Park (just east of the town centre).

It heads north-east as Munnik Avenue to form an interchange with the Polokwane Eastern Bypass (N1 national route) adjacent to the Mall of the North in Bendor Park before exiting the city.

[1] From the N1 interchange, the R81 heads north-east for 71 kilometres, bypassing Sebayeng, to reach a junction with the R36 road north-west of Modjadjiskloof.

[1] From the junction with the R36 near Modjadjiskloof, the R81 goes north-east for 70 kilometres, bypassing the Mooketsi Baobab, to enter the town of Giyani.

[1] From Giyani, the R81 goes north for 47 kilometres, through Malamulele, to end at a junction with the R524 road at Nyavani.