The Presbyterian Board of Foreign Mission had started mission work within the Chinese community in New York City in 1868. In 1885 the Board extended a call to Mr Huie Kin who came as an immigrant to the United States from China at the age of 14 and worked his way through college and seminary, to continue the mission work in New York City Chinatown. Mr Huie started a Sunday School with 12 students in a rented room at 15 University Place. Twenty five years later, on December 18, 1910, the First Chinese Presbyterian Church was incorporated at 223 East 31 Street, with Rev Huie Kin installed as Pastor. Rev Huie Kin retired in 1925 and was succeeded by Rev Dr Kai Chong Yeung who served from 1928 to 1958. Rev William Doo served as Pastor from 1958 to 1963. Rev Eson Tse was installed as Pastor in 1964 and served until 1979. Rev Dr Matthew Lui was invited to be the next Pastor and he served for 23 years until his retirement in 2003. Rev Laura Jervis served as Moderator of The Session from 2003 until 2013 when Rev Nathan Lim was installed as Pastor. Rev Laura Jervis served again as Moderator of The Session from 2018 when Rev Nathan Lim resigned.
In 1951 the church moved to 61 Henry Street, sharing the historic church building with the Sea and Land Church. The church was built in 1819 by the Dutch Reformed Church on land donated by Colonel Henry Rutgers. In 1966 the church building and the 1824 Erben pipe organ were designated as historic landmarks. On February 7, 1974, the Presbytery of New York City officially transferred the great historic church building as a gift to the First Chinese Presbyterian Church to be dedicated to the service of the Chinese community.