Bishop John Shaw established St. John's Seminary in 1915. Early attempts at a seminary had occurred at St. Mary's Parish in San Antonio (1876–78), Guadalupe College in Seguin (1878–80), and St. Joseph in Victoria (1880–1902). St. John's opened first in the chancery building and was moved next to Nuestra Señora de la Purísima Concepción de Acuña Mission in 1920. It was a high school and college from the beginning. A graduate theology department was added in 1928, two years after San Antonio was named an archdiocese. It is believed that St. John's was the only Catholic seminary in the United States where all twelve years were offered at the same site.
Robert E. Lucey was installed as archbishop of San Antonio on March 27, 1941. One of his first major decisions was to invite the Vincentian fathers to administer and teach at St. John's. The old Trinity University campus in the west end of town was purchased. The college and graduate theology students were transferred there in the fall of 1952. The new campus was named Assumption Seminary; St. John's remained as a high school.
The undergraduate students began taking their academic classes at nearby St. Mary's University in 1964. Diocesan priests took over responsibility of administration and pastoral formation in 1967. That same year the graduate theology students began taking their academic classes at St. Mary's University. The theology students transferred to Oblate School of Theology for academic formation in 1970. The undergraduate program began to be phased out in 1975.
In 1990 Assumption Seminary was a house of residence and pastoral formation for students for the Catholic priesthood in a bicultural ministry. All students must make a commitment to Hispanic culture and language. Assumption is the only diocesan seminary in the United States that is connected with a religious house in a collaborative model of education and formation.
Pope John Paul II visited San Antonio on September 13, 1987, and stayed at Assumption that evening. He had lunch there with the Texas bishops and met that evening with about 1,500 Polish people from Panna Maria. Assumption-St. John's concluded seventy-five years of service in 1990. It has produced one martyr, ten bishops, and about 650 priests from its staff and alumni.