The specific scene that Waterhouse bases this painting on occurs in lines 52–65 of the epic poem: There was a cove, a little inlet shaped like a bent bow, a quiet place where Scylla, at midday, sought shelter when the sea and sky were hot; and, in midcourse, the sun scorched with full force, reducing shadows to a narrow thread.

And Circe now contaminates this bay, polluting it with noxious poisons; there she scatters venom drawn from dreadful roots and, three-times-nine times, murmurs an obscure and tangled maze of words, a labyrinth— the magic chant that issues from her lips.

Anthony Hobson describes the painting as being "invested with an aura of menace, which has much to do with the powerful colour scheme of deep greens and blues [Waterhouse] employed so well.

"[5] Circe Invidiosa exemplifies Waterhouse's experimentation with the femme fatale archetype, which pervaded an immense amount of late nineteenth-century art.

However, Chris Woods argues that Waterhouse's portrayals of Circe are not wholly evil, destructive, or monstrous, much like one sees in paintings of female mythological figures by Gustave Moreau or other European Symbolists.