The Secret River was inspired by Grenville's desire to understand the history of her ancestor Solomon Wiseman, who settled on the Hawkesbury River at the area now known as Wisemans Ferry. Her inspiration to understand this came from her taking part in the 28 May 2000 Reconciliation Walk across Sydney Harbour Bridge during which she realised that she didn't know much about the early interactions between the settlers and the Aboriginal people. Initially intended to be a work of non-fiction about Wiseman, the book eventually became a fictional work based on her research into Wiseman but not specifically about Wiseman himself. The novel took five years and twenty drafts to complete.
The novel is dedicated to the Aboriginal people of Australia. Although sparking hostility from some historians it received a positive response from many Aboriginal people, Grenville has said "they recognise that the book is my act of acknowledgement, my way of saying: this is how I'm sorry".
The Secret River has been adapted for the stage by Andrew Bovell; the play was presented by the Sydney Theatre Company in January 2013.