[citation needed] The school was founded in April 1958 by Francis Cardinal Spellman, who purchased the former Poughkeepsie High School building and grounds from the Poughkeepsie Board of Education.

The school was given its name in honor of the centenary of the apparition of the Virgin Mary at Lourdes in France.

The new school opened in September 1958 with a faculty of four brothers and four sisters, and an athletic coach.

The 2014–2015 school year began under the leadership of the new principal, Catherine Merryman, in September 2014.

Our Lady of Lourdes is a member of the New York State Public High School Athletic Association.