Founded in January 1835, in the then-fashionable Bowery section of Manhattan, St. Bartholomew’s began its life as part of the Evangelical movement in the Episcopal Church. Worship services were held in a plain church at the corner of Great Jones Street and Lafayette Place. At first growth was slow, but by 1872 St. Bartholomew’s was large and prosperous enough to build a splendid new church at Madison Avenue and 44th Street. 

Designed by James Renwick, the architect of St. Patrick’s Cathedral, the building was later embellished with a triple portal by Stanford White. It was from the Madison Avenue pulpit that The Rector David H. Greer in 1888, inspired the parish to become a major force for social welfare in the city. 

During the enormous immigration of the late 19th century, St. Bart’s huge parish house on 42nd Street (built with the support of the Vanderbilt family), ministered to large numbers of the new arrivals, who lived in appalling poverty in the tenements of the East ’40s and ’50s. St. Bartholomew’s also became a force in the musical life of the city and the wider church.. Over time, serious structural problems developed in the Madison Avenue building, so the parish commissioned Bertram Goodhue to design a new church on Park Avenue between 50th and 51st streets, St. Bart's current home. 

In 1918, the parish moved into the new building, which was built in the Romanesque style and provided a harmonious setting for the Stanford White portal which had been brought from the old building. As funds and materials were available, the interior was decorated in the Byzantine style with major mosaics in the narthex and over the high altar.  

The Community House, adjoining the church at 50th Street, was built during Rector Robert Norwood’s tenure (1925–32). Well into the 1960s, St. Bart’s was one of the three or four largest congregations in the Episcopal Church. As its immediate neighborhood changed from primarily residential to corporate and commercial, the parish ministry increasingly reached out to the community and non-members. In 1981, a real estate developer offered a plan to build an office tower on the site of the adjacent community house, ensuring a financial endowment of the church's mission and maintenance. 

Conflict developed within the parish and between the church and the city over the designated landmark status of the building. In the calling of a new rector in 1994, church leadership made a commitment to growing St. Bartholomew’s as a congregation, as well as restoring and preserving its landmark building. As a result, attendance and membership increased. As a sacred oasis and designated New York City Landmark and national Historic Landmark.