Authorised by Parliament in 1833 and designed by George Stephenson and Joseph Locke, it opened for business on July 4, 1837, running for 82 miles from Birmingham through Wolverhampton (via Perry Barr and Bescot), Stafford, Crewe, and Warrington before joining the Liverpool and Manchester Railway at Newton Junction. The GJR established its chief engineering works at Crewe.
Shortly after opening, with a temporpary Birmingham terminus at Vauxhall, servcies were routed to and from Curzon Street Station, which it effectively shared with the London and Birmingham Railway (LBR), whose platfoms were adjacent, providing a link between Liverpool, Manchester and London.
In 1840 the GJR absorbed the Chester and Crewe Railway shortly before it opened. Seeing itself as part of a grand railway network, it encouraged the development of the North Union Railway which took the tracks onward to Preston, and it also invested in the Lancaster and Carlisle railway and the Caledonian Railway. In 1845 the GJR merged with the Liverpool and Manchester Railway, and consolidated it's position by buying the North Union Railway in association with the Manchester and Leeds Railway.
The GJR was very profitable, paying dividends of at least 10% from its opening and having a final capital value of over £5.75 million when it merged with the London and Birmingham Railway and Manchester and Birmingham Railway companies to became part of the London and North Western Railway in 1846.