Born in London, Wylie was sent to China in 1847 by the London Missionary Society to be superintendent of its printing press in Shanghai. While engaged in this task, he served as editor for the Shanghai Serial, published from 1857 to 1858. During his time in Shanghai he collected the material needed to publish his noted work Memorials of Protestant Missionaries to the Chinese (1867), which gives bibliographic details on all Protestant missionaries in China from 1807 to the early 1860s. Lists and descriptions of their writings are given in both Chinese and English.
After 1863 Wylie was an agent of the British and Foreign Bible Society (BFBS). He and his colporteurs distributed one million New Testaments in fifteen of China's eighteen provinces and surveyed new areas to be occupied for mission work. When failing eyesight caused him to leave China in 1877, he continued to work with the BFBS in London.