The A758 headed east from Ayr through the valley of the River Ayr to meet the A76 at Mauchline.
The route started on the A719 in Whitletts forking right onto High Road while the A719 followed Low Road, which is now unclassified to the north having been replaced by the A77 Ayr bypass. The route then wound east across farmland to pass through Mossblown on Mauchline Road. A steady climb lifted it to a summit south of Tarbolton, before it dropped back down to the banks of the River Ayr. A straighter section then led it into Mauchline, where it followed Ayr Road before ending on the A76 in the town centre.
The route was originally left unclassified in 1922, but had become the A758 by 1928. It is thought that it may have briefly been numbered as a B road before becoming a Class I route, but to date this has not been confirmed. For many years, the A758 ran unchanged through the Ayrshire countryside. However, with the coming of the A77 Ayr bypass, the A758 was truncated slightly at its western end, with the A719 rerouted to take over the section of A758 within the bypass. The rest of the route has since been downgraded to Class II status, becoming the B743.