The school was the brainchild of Canon Melville Harcourt, the rector of Brooklyn Height's St. Ann's Church. With the support of the rectory, he founded the school in 1965 in the undercroft of the church with a class of sixty-three students.

While Melville Hartcourt might have founded the school, Stanley Bosworth, the school's founding headmaster, embued it with many of the ideas and spirit that the school embodies to this day. He ensured a commitment to a lack of numeric or letter grades, was dedicated to fostering a community of familiarity, and finally demanded the curriculum be rigorous and intellectually stimulating.

As the school expanded, recruiting artists, musicians, and painters to ensure an artistic environment, it began the move to 129 Pierrepont Street. First occupying a few floors, Saint Ann's eventually bought the entire building in 1966.

129 Pierrepont had been a men's club. Built-in 1906 and designed by architect Frank Freeman for the Crescent Athletic Club. The Crescent Club was founded in 1884 by Brooklyn Yale alumni who wanted to form a football team. This building was Crescent's city clubhouse and included a swimming pool, bowling alleys, squash courts, gymnasium, formal dining room, library, and bedrooms. Going bankrupt in the great depression, the clubhouse had various different renters and owners until Saint Ann's moved in.

As Saint Ann's grew and began to be recognized for its achievements, it slowly branched away from the church. The School and Vestry of the church petitioned the state for an absolute charter and in September of 1981, it was granted. In May of the following year, the church and the school formally disassociated. While the two were now officially separate, the two communities remain affiliated and have supported each other over the years.

Many of the school's official functions are still held in St. Ann & the Holy Trinity (the church that the parish moved to in the 1970s.) These events include holiday assemblies, concerts, and graduation.

Though Stanley Bosworth retired in 2003, the school continues to cherish many of the values that he and Melville Hartcourt established in its founding.

Saint Ann's now teaches students from preschool through high school and offers classes on everything from Russian Literature to Puppetry.