Plans to build a railway between London and York were first proposed as early as 1827. Progress was slow and it was not until 1846 the campaign led by Edward Denison was successful and the London & York Bill was passed by Parliament.

Edward Denison became chairman of the Great Northern Railway and William Cubitt was appointed chief engineer. Denison's plans included a direct line from London via Peterborough and branches to Sheffield and Wakefield. The first section of the line, Louth to Grimsby, was opened in 1848. The following year services were operating between Peterborough and Doncaster.

The London terminus at King's Cross was completed in 1852 and by the following year the Great Northern Railway had access to Bradford, Cambridge, Leicester and Nottingham. In 1857 the Great Northern Railway began running express trains between London, Sheffield and Manchester. Other branch lines were opened and by 1860 the railway had reached all the main towns in West Yorkshire. The transport of coal from this area to London provided the Great Northern Railway with substantial revenues.

Edward Denison retired in 1864 and was replaced by Henry Oakley. He appointed F. P. Cockshott as his superintendent and under his direction, the railway gained a reputation for providing a very good service. By the early 1870s the Great Northern Railway was running more express trains than any of its main rivals.