John Williams Waterhouse was born in Rome, Italy, and both of his parents were artists. In the 1850's his family moved to England. John, known by his family as Nino, entered the Royal Academy in 1870, after having assisted his father's studio.

His early works were classical themes in the spirit of Alma-Tadema and Frederic Leighton, and all exhibited at the Royal Academy, the Society of British Artists and the Dudley Gallery.

In 1883 John married and took up residence at the Primrose Hill Studios. By 1888 Waterhouse's interests turned towards those of the Pre-Raphaelites, who portrayed particularly tragic or powerful femmes fatales, as well as plein-air painting.

He was elected an associate of the Royal Academy in 1885 and a full member in 1895.

In the 1890s Waterhouse began to exhibit portraits. In 1901 he and his wife moved to St John's Wood and John joined a social organization that included Lawrence Alma-Tadema and George Clausen. He also served on the advisory council of the Saint John's Wood Art School.

Waterhouse continued to paint until his death in 1917.