The school was founded in 1828 by Zilpah Grant, with assistance from Mary Lyon. Grant had previously been a teacher and Lyon a student at an academy for female students in Byfield, Massachusetts. The school's focus was on preparing girls for careers as teachers and missionaries. It offered a "rigorous curriculum", including study of English, arithmetic, geography, chemistry, human physiology, history, the natural sciences, religion, vocal music, and calisthenics, and placed an emphasis on "standards of personal conduct and discipline". Teachers encouraged students in questioning and analysis, in addition to comprehension. As part of their preparation, students did practice teaching with guidance from a teacher. Enrollment averaged 116 students.
Mary Lyon left as the principal in 1834 to begin a three-year effort that culminated in 1837 with the founding of Mount Holyoke College in South Hadley, Massachusetts. Grant retired from education in 1839, whereupon the school closed. In 1844 it was reopened by Eunice Caldwell Cowles, an Ipswich graduate, and her husband John P. Cowles, a minister. Ipswich Seminary operated until 1876, by which time the increasing availability of public schools had reduced the need for schools of this type. According to Academy records, 88 of school's graduates went on to teach as educational missionaries in the western and southern United States.
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