The school was first organized and recognized in 1904 through Msgr. Donato Guimbaolibot with the assistance of Dr. Jose Lugay. It was named Gloriosa Patriarca San Jose affiliated with Santo Tomas. In 1929, it was named Guiuan Academy with Msgr. Guimbaolibot as Director. On May 1941, on the invitation of Bishop Miguel Acebedo of the Diocese of Catbalogan, the Religious of the Virgin Mary (RVM) took over the administration. These Sisters belong to the first Filipino Congregation founded by a Filipina-Chinise mestiza, Mother Ignacia del Espiritu Santo.

In June 1941, the school admitted students for Elementary and the Secondary courses (First to Second Year). The name was changed to Assumption Academy in August 15, 1941. During the World War II, classes in all levels were suspended. After the war, complete secondary courses was offered. In 1947, the name was changed to Assumption College with courses in Associate of Arts. It was later granted the permits to offer Bachelor of Science in Elementary Education and Bachelor of Arts.

In 1967, on the wish of Bishop Vicente Reyes of the Diocese of Borongan, only girls were admitted to the High School Department. Msgr. Guimbaolibot put up High School for boys. College courses were phased out in 1971-1972 and the Elementary was temporarily suspended for school year 1973-1974 due to few enrollees and financial problems and was phased out in 1974. The name was changed to Assumption Academy of Samar and on 1982 boys were re-admitted.

The academe celebrated its Golden Jubilee under the RVM in 1991. In 1998, the general council under Reverend Mother General Ma. Clarita Balleque, RVM granted the request for the construction of the new building. The ground breaking was done on December 5, 1998 and on June 11, 1999, the initial 10 classrooms were blessed and made ready for the use of the students. It was followed by with the construction of Administrative offices, library, laboratory, canteen and Sister' convent. On December 28, 1999, the first reunion of the Mother Ignacia Club Members was held and followed by a Jubilee Reunion from batch 1950-2000 on December 28, 2000.

On May 23, 2000, the administrative, students services building and the Sisters' Convent were blessed. On the same year, the school was able to purchased 15 new computer units after its contract with the M-SET. Added to these was a new sound system donated by the alumni, and student body organization. Another remarkable event in the school was its changed of name from Assumption Academy of Samar to St. Mary's Academy of Guiuan which was successfully and meaningfully done in October 12, 2000.