In 1651, Petrus Stuyvesant, Director General of New Netherland, purchased land for a bowery or farm from the Dutch West India Company and by 1660 built a family chapel at the present day site of St. Mark's Church.

[6] In 1828, the church steeple, the design of which is attributed to Martin Euclid Thompson and Ithiel Town, in Greek Revival style, was erected.

More changes came about beginning in 1835, when John C. Tucker's stone Parish Hall was constructed,[4] and the next year (1836) the church itself was renovated, with the original square pillars being replaced with thinner ones in Egyptian Revival style.

Later, in 1861, the church commissioned a brick addition to the Parish Hall, which was designed and supervised by architect James Renwick Jr., and the St. Mark's Hospital Association was organized by members of the congregation.

Furthermore, in 1975, the Danspace Project was founded by Larry Fagin; the Community Documentation Workshop under the direction of Arthur Tobier was established; and the Preservation Youth Project expanded to a full-time work training program, which undertook the mission of the preserving St Mark's landmark exterior under the supervision of artisan teachers.

[2] Rector William Guthrie was known to incorporate Native American, Hindu, Buddhist, and Bahá'í ceremonies and guest speakers into services.

In 1919 poet Kahlil Gibran was appointed a member of the St. Mark's Arts Committee, and the next year, the two prominent Indian statues, "Aspiration" and "Inspiration" by sculptor Solon Borglum, which flank the church entry, were unveiled.

It was an inclusive, non-juried group exhibition that featured hundreds of artists from the neighborhood and utilized both the interior spaces and the yard.

Theatre Genesis was founded by director Ralph Cook in 1964 and, in the same year, Sam Shepard had his first two plays, Cowboys and Rock Garden produced at the church.