While attending evening classes at the Glasgow School of Art, Mackintosh was apprenticed to a local architect, John Hutchinson. After completing his apprenticeship in 1888, he joined the firm of Honeyman and Keppie and became a partner in 1904.

In collaboration with three other students (collectively known as “The Four”), one of whom, Margaret Macdonald, became his wife in 1900, Mackintosh achieved an international reputation in the 1890s as a designer of unorthodox posters, craftwork, and furniture. In contrast to contemporary fashion his work was light, elegant, and original, as exemplified by four remarkable tearooms he designed in Glasgow (1896–1904) and other domestic interiors of the early 1900s.

Mackintosh’s chief architectural projects were the Glasgow School of Art (1896–1909), considered the first original example of Art Nouveau architecture in Great Britain; Windyhill, Kilmacolm (1899–1901); Hill House, Helensburgh (1902); the Willow Tea Rooms, Glasgow (1904); and Scotland Street School, Glasgow (1904–06). He was also responsible for two unrealized projects: the 1901 International exhibition, Glasgow (1898), and Haus eines Kunstfreundes, drawings for a competition to design an art lover’s house (1901). The latter was constructed posthumously as House for an Art Lover in the late 20th century in Bellahouston Park, Glasgow. Although all of Mackintosh’s projects have some traditional characteristics, they reveal a mind of exceptional inventiveness and aesthetic perception. By 1914 he had virtually ceased to practice and thereafter devoted himself to watercolour painting.

Although Mackintosh was nearly forgotten for several decades, the late 20th century saw a revival of interest in his work. The stark simplicity of his furniture designs, in particular, appealed to contemporary taste, and reproductions of Mackintosh chairs and settees began to be manufactured. The Mackintosh House in Glasgow was reconstructed and opened to the public as a museum in the late 1970s. In 2018 Mackintosh’s library for the Glasgow School of Art was severely damaged in a fire, just as the building’s restoration from a previous blaze four years earlier was nearing completion.