Harry Mathews nasceu o 14 de fevereiro de 1930 em Manhattan, Nova York, Nova Iorque, EUA. Foi casado com Marie Chaix e Niki De Saint Phalle. Morreu o 25 de janeiro de 2017 em Flórida, EUA.
His father Edward was an important New York architect . Harry was one of the American members of the French literary group l'Oulipo and was a friend of its founder Georges Perec.