Knowing the work of the Brothers of the Christian Schools in Canada, he requested the Brother Superior General to send Brothers to conduct the school. Informed that there were none available with English-speaking skills, the archbishop recruited a few candidates for the Brothers' novitiate with the understanding that, after completing their training in Montreal, they would return to Baltimore to staff the Cathedral school.
Eventually, Brother Francis McMullen, FSC, a native of Baltimore, was assigned as director of the new school on Saratoga Street. He was accompanied by Brother Edward Whitty, FSC. On September 15, 1845, the Brothers assembled 100 students for the celebration of Mass and the opening of what was to become the first permanent foundation of the De La Salle Christian Brothers in the United States.
The steady increase in enrollment eventually necessitated the purchase of a new property at Cathedral and Mulberry Streets. In 1891 Cardinal James Gibbons presided at the dedication and blessing of the new building. He was assisted by Bishop John Keane, rector of The Catholic University of America and a graduate of Calvert Hall. The ceremony included the unveiling of a statue of Lord George Calvert, which would occupy a prominent position on the façade of the new building (and now a replica stands at the corner of Keelty Hall facing the Knott Center).
In September 1960, under the leadership of Brother Gabriel Cannon, FSC, Calvert Hall moved to its current location in Towson. The 32-acre site would allow for the continued growth of its academic and extracurricular programs and accommodate the increasing demand for Catholic, college preparatory education in the metropolitan area. The initial construction consisted of a classroom building, later named Keelty Hall, and the Brothers’ Residence.
Succeeding decades witnessed the construction of a pool building in 1967 (now named Carlo Crispino Center), the Marion Burk Knott Center for the Performing Arts in 1988, the Paul Angelo Russo Stadium and McManus Baseball Field in 1999, and George Young Hall in 2004. In 2007, the dining hall was renovated and enlarged, the Cardinal Shop (formerly the Bookstore) was constructed, the school chapel was renovated, the baseball and practice fields were turfed and Carlo Crispino Stadium was built. The John G. Noppinger ’64 Commons were added in 2015 while the Center for Growth in the Sciences (greenhouse) was dedicated in 2018. The Veterans Tribute was built in 2019 to recognize Calvert Hall's active military members as well as alumni veterans.
The Calvert Hall insignia combines the coats of arms of St. John Baptist de La Salle, founder of the Brothers of the Christian Schools, and the Calvert Family, for whom the school is named.