It is an important road link for the transport of passengers and freight between Sydney and Adelaide and the regions along the route.

It runs generally east–west, roughly aligned to the southern bank of the Murrumbidgee River in New South Wales.

The route now known as Sturt Highway originated from stock routes cut across southern New South Wales through the 19th century: overlanders would travel from Sydney's Main South Road (now Hume Highway) to Albury, and follow along the southern bank of the Murray River to Adelaide.

Edward John Eyre, the English explorer, travelled from Limestone Plains (now Canberra) to Adelaide via this route in 1837, as did Charles Sturt in 1838.

Eyre on his second run to South Australia headed west, following the northern bank of the Murrumbidgee River instead, crossing it at its junction with the Murray close to Boundary Bend, and travelled to Adelaide from there.

[5] The road pioneered by Eyre in 1839 left Hume Highway at Gundagai and followed the northern bank of the Murrumbidgee through the sites of Wagga Wagga, Narrandera, Hay and Balranald, and the north bank of the Murray River through the sites of Euston and Wentworth, passing north of Lake Victoria to the border with South Australia and onwards to Renmark.

6 was declared from Balranald via Euston and Wentworth to the state border with South Australia (and continuing eastwards via Oxley, Booligal, Gunbar, Rankins Springs, Wyalong and Cowra to Bathurst) as part of Mid-Western Highway,[2] and Main Road No.

[22] The passing of the Road Management Act 2004[23] through the Parliament of Victoria granted the responsibility of overall management and development of Victoria's major arterial roads to VicRoads: in 2004, VicRoads re-declared Sturt Highway (Arterial #6610) from the border with South Australia at Murray-Sunset to the border with New South Wales in Mildura.

Work began in January 2007 to upgrade the highway to a four-lane, dual-carriageway road between Gawler Bypass and Greenock in the Barossa Valley.

[25] Northern Expressway was built at the south-western end of Sturt Highway, as part of an AusLink/Government of South Australia project to build a new freeway-standard road, as part of the North–South Corridor project, providing better access for road transport to Port Adelaide and the industrial areas west and northwest of Adelaide.

[26] Other projects in South Australia include a number of overtaking lanes added in the 2000s and 2010s to help make it safer with the high volume of traffic.

The more recent road duplication led to it bypassing Daveyston and Shea-Oak Log instead of passing through these small towns.

[35] To the west and south-west, Sturt Highway crosses the Murray four times: The bridge at Blanchetown was originally opened in 1964.