In September of 1959, Epiphany Catholic School opened in downtown Lake City, in a small hall, offering grade one through four. The Sisters of Mercy, from Wexford, Ireland, staffed the school boasting an enrollment of 29 students. In March 1960 the school relocated to its present site, situated two miles south of downtown Lake City, between Marion St. and U.S. 441. The school is located on twenty acres of land, which includes the church, parish social hall, rectory office, rectory residence, parking lot , playground and natural wooded area.In September 1961, grade five was added with grade six following in 1962; this brought the enrollment to 107. In 1968 the library was added, and the lunchroom modified. The Glander Building was erected in 1974 and was used for music and art classes.

The Sisters of Mercy were recalled to Ireland, and the Sisters of St. Joseph of St. Augustine, were sent to the school. The Diocese of St. Augustine reassigned Sr. Mare Rene Azar and so in 1995 the first lay principal, Mr. J. Mark Akerman was hired. In 1996, Epiphany Catholic School added Kindergarten, with seventh grade following in August 1999, and eight grade added a year later. In 2000, Mrs. Rita Klenk became principal. A new media center, administrative offices, clinic and student bathrooms were added in the summer of 2000. In 2001 a Carmelite Sister joined the staff, and in 2003 Carol Ghionzoli became principal. Rita Klenk took over as principal again in the Fall of 2009.

Today, Epiphany Catholic School serves the community by providing a K-8 program.