In 1926, Patrick Cardinal Hayes entrusted Fr. Edward Marcuzzi the mission of establishing a parish for the Italian-speaking immigrants of Westchester Square area. Fr. Marcuzzi, with pioneering faith proceeded with a handful of parishioners to open a small chapel, under the patronal tutelage of the Blessed Mother, in an empty store located at1605 Parker Street, where the first Holy Eucharistic Mass was celebrated on July 8, 1926. A few months later, in November, the present church was erected and received the State Certificate of Church Incorporation on February 1, 1927.

With Fr. Marcuzzi's death, from 1932 to 1947, Fr. Anthony Profilio, a latin scholar who, like his predecessor, was born, educated and ordained in Italy, served as the second pastor of Santa Maria. Fr. Profilio beautified the church and established many parish societies, such as the Holy Name Society, League of the Sacred Heart, Ladies Auxiliary, St. Theresa and St. Aloysius Societies, Third Order of St. Francis and the Holy Rosary Society. Fr. Profilio also sold several parcels of property to the Apostles of the Sacred Heart Private School and Convent on Zerega Avenue in 1934. After his tenure, Fr. Profilio returned to Sicily as the Vicar General of his Diocese.

Francis Cardinal Spellman appointed Fr. Caldarola who was ordained in 1926, the same year Santa Maria was founded, as the third pastor of Santa Maria. Fr. Caldarola was responsible for a new period in the history of Santa Maria Parish. Within the 25 years as pastor, Fr. Caldarola procured authorization from Archdiocesan officials for the building of the parish school, which was completed in 1951, with the gym and cafeteria in 1957, and the convent in 1964, the latter serving as the residence for the school's teaching sisters belonging to the congregation of the Apostles of the Sacred Heart of Jesus. Fr. Caldarola was named Monsignor in 1957.

With Msgr. Caldarola's retirement in 1957, Terrance Cardinal Cooke appointed Fr. Joseph Adamo as Pastor. Fr. Adamo headed an extensive renovation of the church, which was transformed into one of the most liturgical and up-to-date sanctuaries of the day. Nearly everything in the church was replaced during the redecorating period with the exception of the beautiful stained glass windows (see the photo album) that adorn the sides of the church and the marble altars. In1976, Santa Maria Parish celebrated its Golden Anniversary with a Jubilee Mass celebrated by Cardinal Cooke.

In 1981, Fr. Antimo Fiorillo, who had been an Associate of Santa Maria since 1949 to 1973, succeeded Fr. Adamo as pastor. Fr. Fiorillo made the renovation of the school and the school yard his first priority. The renovation project included a new roof for the school, new cafeteria floor, repavement of the playground and the installation of a new iron fence. He also welcomed to Santa Maria the two largest immigrant communities of the area: the Hispanics and the Filipinos.

With Fr. Fiorillo's retirement in 1993, John Cardinal O'Connor named Fr. John Carbo as pastor. Fr. Carbo took a lead in a making needed renovations in the church building, including the installation of a sound system, and he also had necessary repairs completed in the rectory.

Then, in November 1994, John Cardinal O'Connor asked the Idente Missionaries of Christ Crucified to administer the parish. Fr. Fernando Real M.Id, was named as the first Idente Missionary Pastor of Santa Maria. The primary goal of Fr. Fernando was the unity among the parishioners and their spiritual growth. The spirituality of the parish centers on frequent reception of the Holy Eucharist, where members become one in the Lord, the head of the Mystical Body, the Church. Fr. Fernando also sought to harmonize into a single family the various cultural groups that compromise the Santa Maria community, including the Italian, Hispanic, Filipino, Indian, Vietnamese and most recently Bangladeshi parishioners. After many years of faithful service to the Archdiocese of New York, Fr. Fernando was elected by his Superiors to undertake other important responsibilities within the Congregation of the Idente Missionaries.

During the 85th anniversary year of the parish, Santa Maria parish community received their second Idente Missionary pastor, Fr. Martin I. Esguerra, M.Id, who was called to emulate through perseverance and charity the continuous paternal care of his predecessors.