Professor O'Brien joined Oxford University as Head of Humanities Division in September 2016. Prior to coming to Oxford she was Vice-Principal (Education) and Professor of English Literature at King's College London. She read English at University College, Oxford, took her DPhil at Oxford (St Cross), and was awarded a Harkness Fellowship at the University of Pennsylvania.
She was a research fellow at Peterhouse, Cambridge, and then held posts at Southampton, Cardiff, Warwick and Birmingham universities. Her research focuses on the Enlightenment and eighteenth-century literature, particularly the historical writing and fiction of the period.