Caine was secretary to Dante Gabriel Rossetti, the poet, painter, and leader of the Pre-Raphaelite artists in England, from 1881 to Rossetti's death in 1882. Caine's first novel, The Shadow of a Crime, was published in 1885. It was followed by several others—including The Deemster (1887), The Manxman (1894), The Eternal City (1901), The Woman Thou Gavest Me (1913), and The Woman of Knockaloe (1923). Caine settled in the Isle of Man and sat from 1901 to 1908 in the House of Keys, the lower house of its legislature. He was knighted in 1918 for services as an Allied propagandist in the United States.