Early in 1954 the Wilmington Council of Churches conducted a survey of the Brookside community to determine the need for a Protestant church in the area. In April of that year, the land on which St. Andrew's now stands was deeded to the Board of American Missions of the United Presbyterian Church. In July of that year, Philadelphia Presbytery volunteers established a community church with services held at the Brookside public school building in the shopping center across from the present church site.
February 20, 1955 marked the official organization of St. Andrew's with public recognition of its members, approval of the church's construction, and election of elders and trustees. In 1957 the church became self-supporting, thus no longer a mission church. When a decision was made as to the naming of the church, it was felt the name should says something of the people within and of their responsibility to share the message of Christ. When the members of the congregation were asked to offer suggestions for the name of the church, "St. Andrew's" was chosen as the most appropriate name and description of the congregation, since it calls to mind both the person of Andrew the apostle as well as the Scottish origin of the Presbyterian Church. The apostle Andrew was the first person to join Jesus, having been a disciple of John the Baptist and present at the baptism of Jesus. Andrew then became the first to bring others to Jesus by presenting his brother Peter to the Lord.
In 1958 the United Presbyterian Church of North America merged with the Presbyterian Church, USA and St. Andrew's became a member of New Castle Presbytery. On August 31, 1988, the Rev. Herb Hoeflinger honorably retired after serving almost 30 years as pastor of the church. After some interims and short pastorates, in 2001 the Rev. Dr. John Paderson became pastor and served until June 30, 2016, when he retired.