The author's first novel, Fool on the Hill, was a fantasy that drew on his experiences living in Risley Residential College at Cornell. Published shortly after Ruff graduated from the university, it gained an early cult following which continues to this day. His second book The Public Works Trilogy was postcyberpunk; it helped him to become a fully settled writer. He became fairly well known not only in the United States, but also in Europe.
His third book A Romance of Souls, focuses on multiple personalities; while not technically science-fiction, it nonetheless contains significant speculative elements. The novel was long-listed for the 2005 International IMPAC Dublin Literary Award and won the 2007 James Tiptree, Jr. Award, a PNBA Book Award, and a Washington State Book Award. Ruff is also the recipient of a 2006 National Endowment for the Arts Literature Fellowship in ProseHis latest novel Bad Monkeys was published on July 24, 2007 by HarperCollins. Bad Monkeys received the 2008 Washington State Book Award for Fiction.
He has sold his novel-in-progress, The Mirage, to HarperCollins.