The Manchester Microscopical & Natural History Society grew out of the city's Literary and Philosophical Society, which established a microscopy section in 1858. The club was established under the name 'Manchester Microscopical Society' in order to expand membership to young people and mechanics, offering younger members the chance to own a microscope through a hire purchase scheme. Originally an all-male group, the society admitted women as associate members in 1884.

Members paid a subscription fee, which entitled them to receive a newsletter and reports, and to attend the society's annual Exhibtion, Conversazione and and Soire, as well as meetings. In addition to local members, there were corresponding members based around the world.

In 1955 the society changed its name to the Manchester Microscopical & Natural History Society. Throughout its history the society has had close links to the University of Manchester, as well as with other local microscopy groups such as the Oldham Microscopical & Natural History Society.