Picton Road starts with from the intersection with Old Hume Highway (Remembrance Drive) in Picton, then heads in a south-easterly direction, rossing the Nepean River and then Hume Motorway and continues over grass-forested ranges east of Wilton (passing through Sydney Water Catchment areas) until it ends at the intersection with Mount Ousley Road (Princes Motorway) in the southern fringes of Cataract.

A branch of Main Road 179 was extended from Maldon to the intersection with Hume Highway in Picton on 14 December 1938.

[2] The western end of Trunk Road 95 was truncated the interchange with South-Western Freeway (today Hume Motorway) on 24 October 1984;[8] the eastern end of Main Road 612 was extended along the former alignment from the freeway interchange to Picton (and continuing west via Mowbray Park to Oakdale).

Under this act, the western end of Main Road 612 was truncated to end at Picton on 27 November 2009;[10] Main Road 468 was declared along its former alignment from Picton to Mowbray Park.

With the conversion to the newer alphanumeric system in 2013, this was replaced with route B88 from the interchange with Hume Motorway to the interchange with Princes Motorway (with the rest of the road to Picton left unallocated).