[3][4] Main North Road commences at the interchange with Sturt Highway and continues south into central Gawler as a single carriageway, two-lane road, where it crosses the North Para and South Para Rivers, and the Barossa Valley Way branches to the east between them.

It continues through the outer northern suburbs, passing Salisbury and Mawson Lakes, before eventually reaching the major intersection at Gepps Cross.

In the metropolitan area, Main North Road is a major commuter route to the central business district in the Adelaide city centre.

The portion of Main North Road between the city centre and Mawson Lakes is a 15-minute public transport 'Go Zone', with the maximum wait for a bus being 15 minutes during peak times (7:30 am – 6:30 pm weekdays) and 30 minutes on weekends and evenings.

Main North Road previously continued north past Gawler through Tarlee, Clare, Gladstone and Wilmington, South Australia, then via Horrocks Pass to end at Winninowie, following the route established in the early years of the colony by explorer John Horrocks as a major route for farmers and graziers to reach the capital, passing through rich farmland and the Clare Valley wine region.