In 1861, Harland and Wolff was formed after Edward James Harland formed a business partnership with Gustav Wilhelm Wolff. Previously, Harland had moved to Belfast to become the manager of Robert Hickson’s shipyard in Queen’s Island and, in 1858, Harland bought Hickson’s shipyard for £5,000 resulting in the company becoming Edward James Harland and Company.

The business was a success owing to several innovations, notably replacing the wooden upper decks with iron ones which increased the strength of the ships and giving the hulls a flatter bottom and squarer cross section, which increased their capacity. In 1869, an exclusive business agreement with the White Star Line was drawn up and, in 1874, Walter Henry Wilson and William James Pirrie were recruited as partners of the company.

In 1880, Edward Harland and Company opened its own engine works. Although, due to a government proposal restricting trade and the company's connections with Germany in 1880, it became known as the Queen’s Island Shipbuilding & Engineering Co Ltd. William James Pirrie took over from Harland after his death in 1895. It was during Pirre’s chairmanship in the early 1900s that the company built three renowned ships, the Olympic, Titanic and Britannic.

Political instability in Ireland during 1912, led the company to acquire another shipyard in Govan, Glasgow. It bought the former London & Glasgow Engineering & Iron Shipbuilding Co's Middleton and Govan New shipyards in Govan and Mackie & Thomson's Govan Old Yard, all of which were neighbouring. The three shipyards were amalgamated and redeveloped to provide a total of seven building berths, a fitting-out basin and extensive workshops; enabling them to specialise in the building of tankers and cargo ships. Shortly after, the company purchased the nearby shipyard of A. & J. Inglis and acquired a stake in the company's primary steel supplier, David Colville & Sons. The company also established shipyards at Bootle in Liverpool, North Woolwich in London and Southampton. Although all of these were to close in the 1960s after the company consolidated its operations in Belfast.

During the First World War, the company built the 15-inch gun armed "large light cruiser" HMS Glorious and acquired a shipyard on the eastern side of Musgrave Channel which became known as East Yard and specialised in the mass-production of ships. In 1936, the company expanded into aircraft manufacturing with Short Brothers and, during the Second World War, the company’s workload and workforce dramatically increased; also manufacturing tanks and other artillery components.

A decline in demand for ocean liners coupled with competition from Japan in the late 1950s resulted in the company’s last liners being launched and completed by 1961. As a result of government loans and subsidies to British shipyards in the mid-1960s, the shipyard underwent a modernisation programme enabling it to be used for the building of post-war merchant ships. The 1970s saw the company nationalised and its workforce decline; becoming known as Harland & Wolff Holdings Plc. It was after this that they specialised in the building of standard Suezmax oil tankers.

As a result of the competitive pressures they faced, Harland & Wolff began to focus more on design and structural engineering, as well as ship repair, offshore construction projects and other projects to do with metal engineering and construction; including the construction of several bridges in Britain and the Republic of Ireland. Harland & Wolff's last shipbuilding project was MV Anvil Point, launched in 2003 and used by the Ministry of Defence. In the same year, Harland and Wolff’s parent company sold 185-acres of surplus shipyard land and buildings now know as the Titanic Quarter which includes the Titanic Belfast attraction.

In recent years, Harland and Wolff’s involvement in ship-related work has increased. Most recently, in April 2023, the Belfast yard completed its first new vessel since Anvil Point in 2003. It is a barge for the waste management company, Cory, the first of twenty-three such barges. From 2025, the yard is expecting to complete the final assembly of three naval support ships for the Royal Navy as part of the Team Resolute Consortium