The current A50 runs south-east from Warrington via Junction 20 of the M6, Knutsford, Holmes Chapel, Kidsgrove and Stoke on Trent to Junction 24 of the M1 near Kegworth, via Derby's southern bypass.

The Stoke-and-Derby section was originally intended to be part of an M64 motorway but this project was cancelled in the 1970s.

In November 2013 it was reported that funding would be being made available for improvements to the section around Uttoxeter, with work starting no later than 2015/16.

Part of the route mirrored the plans for the original M64 motorway, with three lanes in some sections – notably between Kegworth and the A6 near Derby.

The new A50 route was opened in stages between March 1985 and 1999, with using various temporary designations: On completion, the Southern Derby Bypass was re-designated as the A50, being maintained privately by Connect A50 Ltd. Much of this new section of road is made of concrete.