The founding of St. Mark's began in 1914, when a small group of worshipers in a private home on Ortega Point established St. Columba’s Mission as an outgrowth of St. John’s Parish in downtown Jacksonville. In 1919, the first services were held near the present site of St. Mark's in a former Army building, with the Reverend Douglas B. Leatherbury as priest-in-charge. In 1922, the mission was organized as a parish and named St. Mark’s. The Reverend Dr. Leatherbury was its first rector.

St. Mark’s has missionary spirit that has spawned three mission churches which are now full parishes: St. Catherine’s, St. Peter’s and The Church of the Epiphany. The church and its associated properties comprise a multifaceted campus incorporating the church, day school with extended day care program, early learning center with church nursery, Christian formation building, library, bookstore and archives center, pastoral care center and youth center. From its small beginnings in 1914, St. Mark's has grown to include 2,000 communicants and 900 families in the following age groups:

0-18 years - 25%
19-40 years - 26%
41-65 years - 32%
over 65 years - 17%

St. Mark’s Episcopal Day School was established as an outreach ministry of the parish in 1970. In 1990, to meet the needs of a growing parish, the church underwent major renovation and expansion. Construction in 1994 added a new 2000 square foot youth center. In 1997, Grace House was dedicated as a pastoral care, hospitality and resource center. In 1998, an Early Learning Center added dedicated church nursery space, classrooms for school pre-kindergarten and extended day programs and a common room/chapel.

St. Mark's has been served by six rectors:

The Reverend Douglas Bagwell Leatherbury, D.D. (1922-1961)
The Reverend Robert Core Clingman (1962-1971)
The Reverend Willis Barnum Coker McCarty, D. Min. (1971-1994) 
The Reverend Paul Hamilton Fuller IV, D. Ed. (1995-1998)
The Reverend Robert Leigh Spruill, M. Div. (2001-2005)
The Reverend Jonathan Bachman Coffey, Jr., M.Div. (2006 -Present)
 
St. Mark’s Episcopal Day School is across the street from the church on 4 ½ acres. Additional construction in 1997 added more classrooms, new computer and science labs, a new early learning center and dedicated church nursery, and growth continues to meet the needs of increasing demands. In January 2000, a single dwelling home adjacent to the school campus was purchased to provide much needed classroom space and to expand the extended day program.
All grounds and buildings are under the stewardship of St. Mark’s Church. Any future renovations or improvements will continue to meet the current and future needs of St. Mark’s parishioners and the community.

The location at the corner of Oxford Avenue and Ortega Boulevard was purchased in 1923. The cornerstone of the present church building was dedicated in September 1942. During the past 84 years, growth and construction have continued with the building of the church parish hall in 1953, church expansion in 1975, and the renovation of the parish hall and other buildings in 1987.