A Dublin-based writer, he is a columnist for Slate, writes for The Millions and is a regular contributor to The New Yorker's Page-Turner blog. His work has been published in The New York Times Magazine, The New York Times Book Review, The Observer and The Independent. He is the author of Epic Fail: Bad Art, Viral Fame, and the History of the Worst Thing Ever. In 2013, his academic monograph on the work of novelist John Banville, John Banville's Narcissistic Fictions, was published by Palgrave Macmillan. He was an Irish Research Council postdoctoral fellow from 2011 to 2012 at Trinity College, where he taught contemporary literature. In 2018 he received the Wellcome Book Prize, endowed with thirty thousand pounds, for his book How to be a machine. The book was selected from six finalists for this award, which commemorates exceptional works of fiction and nonfiction that expose and illuminate in various ways how health and medicine affect our lives. Edmund de Waal, chairman of the jury that awarded him the prize, noted that How to Be a Machine had won because it was "a passionate, entertaining and compelling examination of those who would choose to live forever. Mark O'Connell brilliantly examines issues of technology and uniqueness. In doing so, it focuses on timely issues about mortality, what it might mean to be a machine, and what it really means to be human."