In 1961, Sister Clarice Marquart became principal and continued the long traditions of the school. She was followed in 1962 by Sister Virginia Will, in 1965 by Sister Francine (Sister Mary Kay Stahl ’49), and in 1966 by Sister Leonardine Cosgrove. This was the time of the Second Vatican Council in Rome and many upheavals and changes resulted in the Roman Catholic Church. This also impacted the Academy. In 1963, the school came together tearfully and prayerfully after the assassination of President John F. Kennedy. In 1969, Sister Joanne Cleary was appointed principal and with the increased enrollment, helped to convert some of the convent space for student use.
The deindustrialization of Buffalo began in earnest when the St. Lawrence Seaway made it possible for heavy shipping to bypass the city through the Welland Canal. Shipping-related work began to disappear. This had a domino-like effect: the city lost its place as the grain storage center of the United States as ships went directly to Montreal instead of Buffalo. In turn, grain processing industries closed. It was also an era of social change. The Buffalo School District was ordered to do a better job of integrating black and white students. The University at Buffalo expanded with an additional campus in Amherst, marking a new era of higher education in the region. At the same time, there was social upheaval with the 1967 race riots on the East Side and the 1969 trial of the Buffalo Nine, a group of student activists arrested while resisting the draft by claiming sanctuary in the Unitarian Universalist Church on Elmwood Avenue.