The parish was established in 1915 by Italian immigrants who faced discrimination at Church of the Epiphany, which was located two blocks away on Second Avenue at the corner of East 22nd Street.

[1][2] Masses were originally held in the basement of Church of the Epiphany and in a rented hall at First Avenue and East 23rd Street.

[6] Two years later, the church commissioned architects Salvati & Le Quornik to prepare plans for a four-story rectory and parish hall.

[8][9] The Church of St. Sebastian was spared from demolition by the urban renewal project and the master plan for the new development that would surround the site of the church—East Midtown Plaza—was specifically designed by Davis, Brody & Associates to take the design of St. Sebastian's into account, including the selection of brick colors for the adjacent buildings and making the church a focal point of the new midblock plaza formed by the addition of two cul-de-sacs on East 24th Street.

[12][13][14] The church was demolished and the property was sold to a private developer, who erected an apartment building on the site.