Educated at Millfield School in Somerset and at Brasenose College, Oxford, Mawer took a degree in Zoology and has worked as a biology teacher for most of his life. He published his first novel, Chimera, (Hamish Hamilton, 1989) at the comparatively late age of thirty-nine. It won the McKitterick Prize for first novels. Mendel's Dwarf followed three works of modest success and established him as a writer of note on both sides of the Atlantic. The New York Times judged it one of the "books to remember" of 1998. The option on a film version was sold first to Uzo and then to Barbra Streisand. The Gospel of Judas and The Fall followed, with the latter winning the 2003 Boardman Tasker Prize for Mountain Literature. More recently, he published Swimming to Ithaca, a novel partially inspired by his childhood on the island of Cyprus. A book called A place in Italy (Sinclair-Stevenson, 1992), written in the wake of A year in Provence, recounts the first two years in the village in Italy he went to live in. He has mounted one other foray into the field of non-fiction, Gregor Mendel: Planting the Seeds of Genetics, which was published in conjunction with the Field Museum of Chicago as a companion volume to the museum's current exhibition of the same name.

In 2009, Mawer published The Glass Room, a novel about a modernist villa built in a Czech city in 1928. Mawer has acknowledged that the book was primarily inspired by the Villa Tugendhat which was designed by architect Ludwig Mies van der Rohe and built in Brno in the Czech Republic in 1928-30. The novel was nominated for the 2009 Man Booker Prize.

Mawer has lived in Italy since 1977, teaching biology at St. George's British International School in Rome. He is married and has two children.