In the Odyssey, Ulysses is warned in advance that any sailor who hears the Sirens' song will be drawn irresistibly toward them and to their death. Determined to hear the song himself without succumbing to it, he orders his crew to fill their ears with wax and to bind him tightly to the ship's mast, instructing them to ignore any pleas he makes to be released as the ship passes the Sirens' island. The device lets Ulysses experience the temptation directly while remaining physically unable to act on it, a solution that turns the encounter into as much a study of self-restraint as of danger.

In the earliest classical sources, the Sirens were imagined as part-bird, part-woman creatures rather than the mermaid-like figures later tradition sometimes substitutes. Nineteenth-century British and European painters treated them as one of several dangerous women drawn from classical mythology, a category that also included figures such as Circe and Medusa, women whose power lay specifically in their capacity to lure, transform or destroy men who came too close. This grouping of femmes fatales from myth ran through much of Waterhouse's output and reflected a wider fascination among Victorian painters and audiences with beautiful, threatening women drawn from ancient literature.

Waterhouse trained and exhibited chiefly through the Royal Academy in London, and across his career he moved between subjects drawn from Homer, Ovid, Arthurian legend and Tennyson's poetry rather than settling permanently on any one source. Ulysses and the Sirens, completed in 1891, was one of several Homeric and classical subjects he returned to more than once, part of the same sustained interest in mythological women, dangerous or doomed, that also produced his paintings of Circe, Echo, and the nymphs of Hylas's story.