The Liverpool and Manchester Railway (L&M) opened on 15 September 1830. Work on the L&M had begun in the 1820s, to connect the major industrial city of Manchester with the nearest deep water port at the Port of Liverpool, 35 miles (56 km) away. Although horse-drawn railways already existed elsewhere, the Stockton and Darlington steam Railway had been running for five years, and a few industrial sites already used primitive steam locomotives for bulk haulage, the L&M was the first locomotive-hauled railway to connect two major cities, and the first to provide a scheduled passenger service. The opening day was a major public event. Arthur Wellesley, Duke of Wellington, the prime minister, rode on one of the eight inaugural trains, as did many other dignitaries and notable figures of the day. Huge crowds lined the track at Liverpool to watch the trains depart for Manchester.

The trains left Liverpool on time and without any technical problems. The Duke of Wellington's special train ran on one track, and the other seven trains ran on an adjacent and parallel track, sometimes ahead and sometimes behind the duke's train. Around 13 miles (21 km) out of Liverpool the first of many problems occurred, when one of the trains derailed and the following train collided with it. With no reported injuries or damage, the derailed locomotive was lifted back onto the track and the journey continued. At Parkside railway station, near the midpoint of the line, the locomotives made a scheduled stop to take on water. Although the railway staff advised passengers to remain on the trains while this took place, around 50 of the dignitaries on board alighted when the Duke of Wellington's special train stopped. One of those who got off was William Huskisson, former cabinet minister and Member of Parliament for Liverpool. Huskisson had been a highly influential figure in the creation of the British Empire and an architect of the doctrine of free trade, but had fallen out with Wellington in 1828 over the issue of parliamentary reform and had resigned from the cabinet. Hoping to be reconciled with Wellington, he approached the duke's railway carriage and shook his hand. Distracted by the duke, he did not notice an approaching locomotive on the adjacent track, Rocket. On realising it was approaching, he panicked and tried to clamber into the duke's carriage, but the door of the carriage swung open, leaving him hanging directly in the path of the oncoming Rocket. He fell onto the tracks in front of the train, suffering serious leg injuries, and dying later that night.

The Duke of Wellington felt that the remainder of the day's events should be cancelled following the accident at Parkside, and proposed to return to Liverpool. However, a large crowd had gathered in Manchester to see the trains arrive, and was beginning to become unruly. Wellington was persuaded to continue to Manchester. By the time the trains reached the outskirts of Manchester the crowd had become hostile and was spilling onto the tracks. With local authorities unable to clear the tracks, the trains were obliged to drive at low speed into the crowd, using their own momentum to push people out of the way. Eventually they arrived at Liverpool Road railway station in Manchester to be met by a hostile crowd, who waved banners and flags against the duke and pelted him with vegetables. Wellington refused to get off the train, and ordered that the trains return to Liverpool. Mechanical failures and an inability to turn the locomotives meant that most of the trains were unable to leave Manchester. While the Duke of Wellington's train left successfully, only three of the remaining seven locomotives were usable. These three locomotives slowly hauled a single long train of 24 carriages back to Liverpool, eventually arriving six and a half hours late after having been pelted with objects thrown from bridges by the drunken crowds lining the track.

The death and funeral of William Huskisson caused the opening of the railway to be widely reported, and people around the world became aware that cheap and rapid long-distance land transport was now possible for the first time. The L&M became extremely successful, and within a month of its opening plans were put forward to connect Liverpool and Manchester with the other major cities of England. Within ten years, 1,775 miles (2,857 km) of railways were built in Britain, and within 20 years of the L&M's opening over 6,200 miles (10,000 km) were in place. The L&M remains in operation, and its opening is now considered the start of the age of mechanised transport; in the words of industrialist and former British Rail chairman Peter Parker, "the world is a branch line of the pioneering Liverpool–Manchester run".