In 1914 the NSW section of the highway was declared a main road.Until it was named the Hume Highway in 1928 it was known as the "Great South Road" in NSW and "Sydney Road" in Victoria.

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The Hume Highway, inclusive of the sections now known as the Hume Freeway and Hume Motorway, is one of Australia's major inter-city national highways, running for 840 kilometres (520 mi) between Melbourne in the southwest and Sydney in the northeast.

From north to south, the road is called the Hume Highway in metropolitan Sydney, the Hume Motorway between Prestons and Berrima, the Hume Highway elsewhere in New South Wales and the Hume Freeway in Victoria.

In addition to these bypasses the sections between Casula (in southwestern Sydney) and Berrima (built 1973–92), and Broadford to Wallan (1976), which both were constructed as major deviations, are also of full freeway standard.

The entire section in Victoria is categorised as a freeway by government roads authority Vic Roads, although there a few intersections along the route that are not yet grade-separated.

The coast of New South Wales from the Queensland border to the Victorian border is separated from the inland by an escarpment, forming the eastern edge of the Great Dividing Range. To climb from the coast to the tablelands the Hume Highway uses the Bargo Ramp, a geological feature which provides one of the few easy crossings of the escarpment.

In the first twenty years of European settlement at Sydney (established 1788), exploration southwest of Sydney was slow.

Although the full length of the Hume Highway is dual carriageway (with at-grade intersections and restricted entry from adjoining land), there are considerable lengths of the highway which are of full freeway standard.

Most of these sections are bypasses of the larger towns on the route, where the need to deviate the route to construct the bypass made it practical to deny access from adjoining land and thus provide full freeway conditions.

This re-numbering for the first time in over 20 years created one continuously signed route along the Hume Highway, having already been signed the M31 in Victoria during the 1990s.

During 2013, the route between Berrima and Prestons was also renamed the Hume Motorway.

The present route of the Hume Highway is much the same as that used by the pioneers.