The order expanded to rural Smithtown in 1929 with the establishment of Mount St. Francis Novitiate and Normal School, having acquired Mill House, an already old property dating back to the first half of the 19th century, in 1928.

The ground-breaking marks the founding of St. Anthony's and its date appears on the school's crest.

The school continued to grow, both in enrollment and with additional facilities on the Smithtown campus until 1984.

On December 5, 1983, Most Reverend John R. McGann announced that, as part of extensive changes in the educational plans of the Roman Catholic Diocese of Rockville Centre, Holy Family Diocesan High School, South Huntington, New York, would close in June 1984, and St. Anthony's High School will re-locate in the Holy Family facility.

Honors and Advanced Placement courses are offered to students who qualify, with electives in all disciplines.