The R59 begins at a t-junction with the R64 west of Dealesville. It heads north to the town of Hertzogville, where it meets the R708 at a t-junction next to the Palmietpan and they become co-signed northwards. North of the town the R59 turns right and becomes its own road north-east to Hoopstad where on the southerly outskirts, before the Vet River, it meets the northern terminus of the R700 at a t-junction and turns northwards. It crosses the Vet River into Hoopstad, where it meets and becomes cosigned with the R34. They loop to the north of the town and turn east before the R59 becomes its own road just north of the Tikwana suburb to resume its journey north-east and continues to cross the R505 before Bothaville. The route continues past a place named Misgunst to reach a t-junction with the R30 and co-sign with it northwards, crossing the Vals River into the town centre of Bothaville. In Bothaville Central, the R727 t-junctions the R30/R59 co-signage. At a four-way intersection north of Bothaville, as the R504 is the road westwards and the R30 continues northwards, the R59 becomes the road to the east. The R59 continues in a north-easterly direction, bypassing Viljoenskroon to the north, where it meets the R76 at a 4-way-junction. Continuing north-east from Viljoenskroon, the route meets the southern terminus of the R501 before going toVredefort. After bypassing Vredefort to the west, it meets the northern terminus of the R721 north of the town. It continues to Parys from the south-west, where it becomes the main road through the town and meets the southern terminus of the R53 and R500 routes from the NorthWest Province. It is not one direct road through Parys. From Parys, the route continues north-east to meet the south-western terminus of the R42 Road extension just before meeting the N1 Kroonvaal Toll Route & crossing over it just north of its Vaal Toll Plaza. It crosses the N1 as a dual carriageway. It proceeds east-north-east, still following the Vaal River, to enter Sasolburg's northern suburbs, where it forms a large interchange with the R57 Golden Highway. It crosses over the R57 and continues north-east to meet Ascot-on-Vaal Road on the outskirts of Sasolburg before crossing the Vaal River into Gauteng province east of Vanderbijlpark as the Sybrand van Niekerk Freeway. It is a freeway for its remainder.
After crossing the Vaal, it interchanges with and crosses the R42 for the second time east of Sharpeville, Vanderbijlpark and south-west of Vereeniging Central, before crossing the R28 from Sebokeng. It continues north and meets the R54 to the Three Rivers suburb and R82 to Vereeniging Central at an interchange close to Duncanville. Two further interchanges with the M61 follow as it continues north-east, passing to the west of Meyerton, intersecting with the R551 during this time. It continues north-east, passed Henley on Klip and intersecting with the R557. It continues north, passing to the west of Garthdale, where it crosses the R550 Road and then the Klip River. Its next major interchange is with Klip River Drive outside Brakendown and Thokoza. It continues into Brakenhurst, a suburb of Alberton, where it crosses the R554 Road and Michelle Avenue in Meyersdal. After a short distance, it meets the N12 Highway at the Reading Interchange and then proceeds to end at a t-junction with the M38 Road in Tulisa Park, Johannesburg South.
