The Route begins at Bapsfontein, Ekurhuleni, Gauteng at the 4-way intersection with the R25 Route and the R50 Route. As Pretoria Road, it heads south-south-west for 10km up to Petit, where it meets the M44 Metropolitan Route and continues by way of a left turn to become Geldenhuys Street southwards. After 4km, the R51 continues by way of a right turn at Aloe Road to become Kingsway Road, bypassing Benoni Farms. As Kingsway Road, it makes up the western border of Daveyton, separating it from Benoni Farms, before crossing the N12 Highway. Just after the N12 Crossing, the R51 is joined by the R29 Route from Benoni Central and they are one road southwards for 5km before splitting in the vicinity of Springs. By Wright Park, at the eastern terminus of the R554, the R51 turns eastwards and by Springs Country Club, the R51 turns southwards. From Springs, the R51 crosses the N17 Highway and makes a 20km journey south to Nigel. From Springs to Nigel, the R51 is followed by and is parallel to the M63 Metropolitan Route. In Nigel, at the main 4-way junction before the Glenverloch Suburb, the R51 joins the road going east and is cosigned with the R42 Route and the R550 Route for 2 kilometres, making up the northern border of the Nigel CBD. At the BalfourRoad Junction, the R51 and the R550 split from the R42 Road to become the road heading south-east. After the Laversburg suburb, just after crossing the Blesbokspruit, the R550 becomes its own road eastwards, leaving Balfour Road with the R51 designation.
From Nigel, the R51 makes a south-south-easterly 33km journey, crossing into Mpumalanga Province, meeting the R548, to Balfour. It enters Balfour southwards as Joubert Street, before turning east, then south at Dyer Street to cross the Balfour Railway southwards. After the Railway crossing, it makes a right turn at Johnny Mokoena Drive and then a left turn to become Joubert Street again. South of Balfour, the R51 meets the bypassing R23 Heidelberg-Standerton Road at a roundabout. From Balfour, The R51 makes a southward 40km journey, passing Grootvlei and its power station, making a left turn, to end at the N3 Johannesburg-Durban Highway. It meets the eastern end of the R54 Route from Vereeniging at the same place.
