Pearl Comfort Sydenstricker was born in Hillsboro, West Virginia on June 26, 1892h. Her father Absalom Sydenstricker and her mother Caroline Stultry were both Southern Presbyterian missionaries. Although she was born in the United States, her parents had been living in China since their marriage in July 1880. Three months after their daughter's birth, the Sydenstrickers returned to China, taking the child with them. The young Pearl Sydenstricker grew up bilingual, learning English from her parents and Chinese from a local tutor.