Since the 40s, there had been talk of providing UK astronomers with a telescope large enough to allow them to compete on equal terms with their counterparts abroad, especially in the USA and Russia. It was eventually agreed that a 100-inch telescope would be constructed, funded jointly by the Treasury and the Admiralty. The telescope would be for the use of all UK astronomers and located at Herstmonceux (Sussex, UK), where the Royal Greenwich Observatory had been moved in the 1950s. In 1967, Her Majesty the Queen performed the opening ceremony for the new Isaac Newton Telescope at Herstmonceux.

But after a number of years it became clear that better astronomical weather conditions than the UK would benefit the astronomical use of the INT. A large telescope is used to look at the faintest, most distant objects and to glean as much information as possible about them. Hence it requires the very best observing conditions that can be obtained. Such conditions are found on La Palma, and therefore it was decided in the early 1970's to move the telescope to its current location on the Roque de Los Muchachos Observatory where it resumed operation in 1984. The re-installation of the telescope was also used to modernise its instrumentation and provide the telescope out with a new, high-quality primary mirror.

The INT was officially re-inaugurated on 29 June 1985, when the inauguration of the Canary Islands observatories took place in the presence of the monarchs and members of the Royal Families of five European countries, and the Presidents of another two.

Since its first operation on La Palma, the role of the telescope has been as a facility for wide-field imaging and intermediate to low dispersion spectroscopy, and the scientific impact of the telescope is as high as that of the best telescopes of its kind.