In the early 19th century, Western colonial expansion occurred at the same time as an evangelical revival - the Second Great Awakening - throughout the English-speaking world, leading to more overseas missionary activity. The nineteenth century became known as the Great Century of modern religious missions.

Beginning with the English missionary Robert Morrison in 1807, thousands of Protestant men, their wives and children, and unmarried female missionaries would live and work in China in an extended encounter between Chinese and Western culture. Most missionaries represented and were supported by Protestant organizations or denominations in their home countries. They entered China at a time of growing power by the British EIC, but were initially restricted from living and traveling in China except for the limited area of the Thirteen Factories in Canton, now known as Guangzhou, and Macau. In the 1842, in the Treaty of Nanking that ended the First Opium War, missionaries were granted the right to live and work in five coastal cities. In 1860, the Treaty of Tientsin (Tianjin) that ended the Second Opium War with the French and British opened up the entire country to missionary activity.

Protestant missionary activity exploded during the next few decades. From 50 missionaries in China in 1860, the number grew to 2,500 (counting wives and children) in 1900. Fourteen hundred of the missionaries were British, 1,000 were Americans, and 100 were from continental Europe, mostly Scandinavia. Protestant missionary activity peaked in the 1920s and thereafter declined due to war and unrest in China. By 1953, all Protestant missionaries had been expelled by the communist government of China.