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The Leeds and Bradford Railway Company (L&BR) opened a railway line between the towns on 1 July 1846. It extended its line from Shipley through Keighley to Skipton and Colne, in 1847 and 1848. While the extension was being constructed, the L&BR negotiated with the Manchester and Leeds Railway, with a view to leasing its line to the M&LR. George Hudson, the so called Railway King, was chairman of the rival Midland Railway at the time and by controversial means, secured the lease of the L&BR for his own company in 1846. Five years later the Midland Railway took over the L&BR company. The former L&BR network was used by the Midland Railway for its own extension to Carlisle, and with allied companies, into Scotland, and as the original core line became busier and more congested, widening schemes were implemented. The first Leeds terminal station has long been superseded, and the line between Skipton and Colne was closed in 1970, but most of the original network continues in use at the present day.

In the early nineteenth century Bradford was the seat of the British woollen industry, and the greatest wool centre in the world. The difficulty for Bradford was the poor state of transport links, although there had been a Bradford Canal from 1774. Conveyance of raw materials in and finished goods out by animal power was slow and expensive. In 1840 the best passenger connection between Bradford and the railway network was at Brighouse, over 6 miles away: the demand was such that 40,000 passengers annually used the horse drawn coach link in 1844. In the early part of the 1830s, the North Midland Railway was being planned; it was to run from Derby to Leeds; the merchants of Bradford asked the NMR company to extend to their town. However the directors of the NMR stated that building a 72 mile railway was already quite enough for them, and they declined. George Stephenson was the engineer of the NMR and advised the Bradford people that forming their own company for a line would be a practical way forward, but this advice was not acted upon.

In reaction to the lack of progress, business interests in Bradford decided to form their own company, and they considered themselves fortunate to secure the services of George Stephenson as engineer, and of George Hudson as chairman. Their company's act of Parliament, the Leeds and Bradford Railway Act 1844, obtained royal assent on 4 July 1844. This was achieved in the face of opposition from rival groups, one of which intended to use atmospheric traction to overcome the difficulty of the steep gradients their line would involve. As part of the Parliamentary process of gaining authorisation, the Leeds and Bradford promoters undertook to build extensions from Shipley to Keighley and from Bradford to Halifax. The authorising act also provided for a new Wellington Station in Leeds together with a connection to the North Midland Railway at Hunslet. On 30 May 1846 the contractor had substantially completed the construction of the line, and arranged a day excursion from Hunslet Junction, Leeds to Bradford for the directors and their friends. The formal opening took place on 30 June 1846, and the general opening to the public followed on 1 July 1846. There were no intermediate stations at first. The Bradford station was referred to as "Market Street" until its name was changed to Forster Square in 1924. Public services began between Leeds and Bradford on 1 July 1846 with a regular hourly service, 18 trains per day in each direction on a weekday with five each way on Sundays. Now the people of Bradford saw that they had another chance, and they petitioned the new Midland Railway to build a branch line to their town. Once again they were rebuffed, as the Midland board said that they "had enough irons in the fire" with the Nottingham to Lincoln line and the Syston to Peterborough line. Stretton comments that as far as Hudson's conduct was concerned, it "shook his reputation to the very foundation and proved to be the turning point, the beginning of the end of Mr Hudson's great and remarkable railway career".

The Leeds and Bradford Railway had been authorised in 1844, and in the following Parliamentary session it obtained authorisation to extend from Shipley to Skipton, there turning south westward to Colne, where it would make a junction with the East Lancashire Railway. The ELR would give a through connection to Manchester and Liverpool. Another independent company was being projected at this time, the North Western Railway, which was planned to form a junction with the Leeds and Bradford extension line at Skipton, and continue west to Morecambe Bay, making a junction en route with the Lancaster and Carlisle Railway. The Midland Railway's alliance with the Leeds and Bradford Railway was proving fruitful, by giving access to these proposed connecting lines. This was authorised by the Leeds & Bradford (Shipley—Colne Extension) Railway Act, of 30 June 1845. This was an authorising Act, but there was never separate company for the extension: the L&BR was leased to the Midland Railway. The extension was opened in stages. The 6 mile line from Shipley to Keighley was ready for the Board of Trade inspection by Captain Simmons, which took place on 13 March 1847. Simmons approved the line for opening, and it did so on 16 March 1847. The line from Keighley to Skipton, 9 miles, was inspected on 28 August 1847, and opened on 8 September 1847.,

In August 1848 both the East Lancashire Railway and the L&BR had agreed that each would work its own line to Colne, and in the following month details were agreed as to the joint station there, which was to be built by the Leeds and Bradford Company. The line between Skipton and Colne opened on 2 October 1848. Although the line was useful in connecting intermediate communities to the railway network, it was seen as primarily a through route between Yorkshire and Lancashire.

As the Leeds and Bradford Railway was the first line in the area through which it ran, many later railways connected into it or branched from it.

At the height of the railway mania, promoters saw that a railway connection might be fruitful between Skipton, shortly to be connected to the Leeds and Bradford Railway, and the Lancaster and Carlisle Railway, under construction and promising a connection to Scotland. The North Western Railway was incorporated on 26 July 1846 to build such a line to Low Gill in what was then Westmorland, now Cumbria. The company was unconnected with the London and North Western Railway, and is often referred to informally as the "Little" North Western Railway. The company found it impossible to fund the ambitious construction, and it opened only from Skipton to Ingleton on 30 July 1849.

Earlier schemes having failed, local interests proposed a railway in the Worth Valley and the Midland Railway agreed to operate it. After much delay in construction, the line opened as the Keighley and Worth Valley Railway on 13 April 1867. The Keighley station was on the Skipton side of Bradford Road level crossing; that was converted to a bridge in 1879 and the Keighley station was moved to the Leeds side of the bridge with separate platforms for Worth Valley trains on 6 May 1883.

In 1868 a station was opened at Manningham, on the northern margin of Bradford. At first simply a suburb, it quickly developed into a conurbation in its own right, housing Manningham Mills, built in the 1870s and forming Europe's largest silk spinning mill. In 1890 the Market Street terminus at Bradford was redeveloped as a six platform station.

The Great Northern Railway opened a line from Bradford to its own terminus at Shipley, in 1874. The GNR ran alongside the Midland line at Shipley, but although a connection was made (on 1 November 1875), through running was discouraged for many years.

The North Western Railway remained an insignificant minor railway, only reaching from Skipton to Ingleton on the Lancaster and Carlisle main line. The Midland Railway had pinned its hopes on reaching Carlisle over the NWR and the Ingleton connection; the LNWR as successor to the Lancaster and Carlisle Railway did all it could to frustrate this use of the line, and at length the Midland Railway decided to construct its own line to Carlisle: the Settle and Carlisle Line. The Midland had leased the North Western Railway from 1 January 1859, and absorbed it on 1 July 1871. The Carlisle line started at Settle, bringing the Leeds and Bradford line and its extension to Skipton onto a new main line. It opened on 2 August 1875 for goods and on 1 May 1876 for passengers.

The Midland Railway and the North Eastern Railway agreed to construct a joint railway between Otley and Ilkley, the Otley and Ilkley Joint Railway. The NER built its own connection to Otley from Arthington, and the Midland Railway opened a connection from the former Leeds and Bradford at Apperley Junction to form a triangular junction at Milner Wood and Burley in Wharfedale, giving connection to Otley and Ilkley respectively. The lines opened on 1 August 1865 to passengers, 1 October 1866 to goods. The Midland Railway opened a direct line from Shipley (Guiseley Junction) to Guiseley forming a triangular junction off the original Leeds and Bradford main line, opening it on 4 December 1876. However the service was withdrawn after 30 April 1876 so that the Pullman cars could be used on the new Settle and Carlisle line.

Local passenger services on the Skipton to Colne section were handled by diesel multiple units from 4 January 1960, and most trains on the route were dieselised from 6 March 1961. The final ordinary passenger service on the Skipton to Colne route was on 1 February 1970, but an enthusiasts' special ran the following day. The former Midland Railway station at Colne was later demolished. As a terminus from the Burnley direction, it was provided with a minimal one platform facility, having no descent from the Leeds and Bradford Railway.