Documents from 1847 signed by Joseph Locke, Sturges Meek and Mackenzie, Brassey & Stephenson show elevations, plans and sections for bridges on line.

A direct route to Preston from Lostock Hall was opened on 2 September 1850 and a branch line from Ormskirk to Rainford Junction via Skelmersdale on 1 March 1858.

Under L&YR ownership, it became the company's main line from Liverpool to Preston & East Lancashire and carried through express trains to Blackpool and Scotland via Blackburn, Hellifield and the Settle-Carlisle Line as well as significant quantities of freight to the docks in Liverpool.

The southern end of the route was subsequently electrified by the L&YR in stages between 1906 (as far as Aintree) and 1913 (through to Ormskirk).

The two sections meet at Ormskirk station on the same alignment but are now separated by buffers in a rare type of cross platform interchange.