In the early 1990s, in the wake of the Fatwah against Salman Rushdie and the continuing troubles in Northern Ireland, Wilson published a pamphlet Against Religion in the Chatto & Windus CounterBlasts series. He wrote biographies of Jesus and St Paul, and a history of atheism in the 19th century entitled God's Funeral, describing its growth as due to influences ranging from David Hume to Sigmund Freud. These and many other of his books such as those on Leo Tolstoy (Whitbread Award for best biography of 1988), C. S. Lewis, Hilaire Belloc are simultaneously sympathetic to religious belief and critical of it.

Wilson was born in Stone in Staffordshire to a Father who became the managing Director of Wedgwood, the pottery company. He was educated at Hillstone School, Great Malvern in Worcestershire, and Rugby School from the age of 13, where he read Mao and Marx in his spare time. While at Rugby, he wrote an article for the school magazine arguing that public schools should be abolished. The national press became interested in the story, with the Daily Express headlining its account "Red rebel in Tom Brown's school". "Reporters arrived at the school gates, wanting to interview me, but my housemaster, wisely, would not let me talk to them," Wilson told Hunter Davies in 1993. After New College, Oxford, he taught English at Merchant Taylors' School, Northwood for two years and then spent seven years as a lecturer in medieval literature at St Hugh's College and New College, Oxford. He married the Shakespearean scholar Katherine Duncan-Jones in 1971. They had two daughters, Emily Wilson (born 1971) and Beatrice "Bee" Wilson (born 1974), and divorced in 1990.

In 2001 Wilson published Dante in Love (2011) presenting a study of the great Italian poet, Dante Alighieri, as an Artist and Philosopher, also depicting an in-depth portrait of medieval Florence to help readers understand the literary and cultural background which engendered the Tuscan's masterpiece, The Divine Comedy.

In addition to his many biographies, Wilson has written three books covering entire eras, The Victorians (2002), After the Victorians (2005), and The Elizabethans (2011), the latter described as "the exhilarating story of the Elizabethan age". Significant novels of Wilson include Scandal about the Profumo affair, The Vicar of Sorrows about a clergyman who has lost his faith dealing with the death of his mother, and Dream Children about paedophilia. His 2007 novel Winnie and Wolf was long-listed for the Man Booker Prize.

In August 2006, Wilson's biography of John Betjeman was published. It was later discovered that another biographer, Bevis Hillier, had sent him a forged letter which was included in the book.

Wilson's biography Charles Darwin, Victorian Mythmaker, (2017), was criticised by John van Wyhe in the New Scientist for confusing Darwin's theory of natural selection with Lamarckism at one point, as well as other scientific, historical and editorial errors. Kathryn Hughes in The Guardian wrote it is "cheap attempt to ruffle feathers", with a dubious grasp of science and attempted character assassination. In The Evening Standard, Adrian Woolfson says that "..while for the greater part a lucid, elegantly written and thought-provoking social and intellectual history" Wilson's "speculations on evolutionary theory," produce a book that is "fatally flawed, mischievous, and ultimately misleading". Steve Jones, an emeritus of University College London, commented in The Sunday Times: "In the classic mould of the contrarian, he despises anything said by mainstream biology in favour of marginal and sometimes preposterous theories." The Geneticist and former Editor of Nature, Adam Rutherford, called the book "deranged" and said Wilson "would fail GCSE biology catastrophically."

The Times (London) called his book Resolution ‘a work of genius’.

Kathryn Hughes wrote in The Guardian of Wilson’s biography of Queen Victoria, Victoria: A Life, ‘Subtle, thoughtful ... a shimmering and rather wonderful biography.’ Daisy Godwin in The Sunday Times review stated that, ‘This won't be the last biography of Victoria but it is certainly the most interesting and original in a long time’.