In 1859 Bishop William Elder responded to the spiritual needs of about 300 Catholics living around Biloxi’s Back Bay area with the establishment of a mission parish, which was served throughout its first years by priests from Nativity B.V.M.(Biloxi), St. Alphonsus (Ocean Springs) and St. Michael (Biloxi) Parishes.

On October 6, 1921, Bishop John Gunn appointed Fr. Patrick Carey as Sacred Heart Parish’s first resident pastor.  Under his leadership, the parish school named for St. Therese, the Little Flower of Jesus, was opened in 1927 staffed by Vicksburg Sisters of Mercy.  Fr. Carey was succeeded by Fr. Dennis O’Sullivan, 1931-38, and Fr. Isidore Fussnecker, 1938-39.

During Fr. Patrick McAlpine’s pastorate, 1939-67, the parish began to grow rapidly with the advent of World War II and the expansion of Keesler Air Force Base.  Still in use during Fr. McAlpine’s pastorate was the wood frame church, dedicated on October 22, 1884, to accommodate 300 people.

Bishop Joseph Brunini dedicated the new church on November 23, 1970.    The new Sacred Heart Elementary School and parish hall were also constructed and dedicated on February 10, 1974, and a parish gym/recreation center was constructed in 1980 all under the pastorate of Msgr. Francis Farrell.  In 2005 Sacred Heart Catholic Elementary received extensive damage from Hurricane Katrina. The school was renovated and re-opened their doors January 2007.  Most recently the bell tower which was damaged in Hurricane Katrina was rededicated December 24, 2017. The bell tower was originally commissioned in 1969, during Msgr. Farrell's pastorate, but not erected until the church was completed in 1971.

Since 1980, Fr. Gerald Cleary, Fr. Patrick McDermott, and Fr. Bob Higginbotham have served as pastors.  Fr. Dominic Pham became pastor in March of 2017.

The Sisters of Mercy have been a part of the parish staff since 1927.