The original scheme for a new road through the rural area south of Manchester was the design of the urban planner Richard Barry Parker, who envisaged the creation of a parkway – a broad, landscaped highway – to run from the new garden suburb of Wythenshawe, connecting it with Manchester City Centre.

This layout was known as the 'Brodie' system, a new approach to road design that had been pioneered in Liverpool by John Alexander Brodie.

To enable this work, Parker's landscaping was removed, with 50,000 trees and shrubs being uprooted, and pedestrian footbridges were installed, and an old country house, Kenworthy Hall, was demolished.

It then shares a short section with the A34 (Oxford Street) running west until St Peter's Square.

Between the M56 and M60, the road has two intermediate junctions; with the B5166 towards Northenden and Sale Moor, and with the A560 leading to Gatley, Wythenshawe and Baguley.

At the southern end, at the A560 junction, the A5103 seamlessly becomes the mainline of the M56 heading towards Manchester Airport, Chester and the M6 motorway.