Born in Rome, Waterhouse's parents, both English artists, nurtured his artistic talent and love of classical subjects. Upon his family's return to England in 1870, Waterhouse attended Royal Academy Schools. The artist's early work, historical genre in ancient settings, was strongly influenced by the work of Sir Lawrence Alma-Tadema.

Throughout his career Waterhouse painted romantic and poetic subjects, often featuring women characterized by their wistful expression and haunting sensuality. Waterhouse was strongly influenced by the work of the Pre-Raphaelite Brotherhood and adapted many of their classical and literary themes for his own compositions. The densely atmospheric works of Waterhouse's mature style is characterized by bold brushwork and a rich, opalescent palette.

Later in his career the artist advanced to a looser style, distinguished by a lighter palette and an increasingly refined handling of paint. During his lifetime, the artist enjoyed a high level of success and frequently exhibited at the Royal Academy. Waterhouse enjoyed the support of many distinguished patrons and his work was collected by British and Australian museums. The artist worked up until his death in 1917, leaving his final work, The Enclosed Garden unfinished.