In some places, the highway has been deviated several times since the first rough track was made between Sydney and Melbourne in November 1842.

[1] Since the time of the first track, the route of what is now the Hume Highway has been the main road link between the Australia's two largest cities – Sydney and Melbourne.

The section of the Hume Highway between the Cross Roads, at Prestons on Sydney's southwestern fringe, and the Medway Rivulet near Berrima, was completely superseded in the period 1973–1992 by a new route built as a freeway.

The main features of this section of the highway were a deep, narrow cutting and the reinforced concrete bowstring arch bridge over Hillas Creek.

North of Albury, a major deviation of the highway was constructed in the 1930s due to the inundation of the original route caused by the raising of the wall of the Hume Dam on the Murray River.

Parts of the old route are visible when the waters of Lake Hume are low from the air and satellite imagery (Google Map)