The church's burial ground dates to the settlement of the New Sweden colony in 1638. When the church was built some sixty years later, care was taken not to build the church on any of the existing graves. Since the earliest graves were marked only with wooden crosses--many of which disappeared over time--it is likely that some of the first graves are underneath the church. It is estimated that the cemetery contains between 8,000 and 10,000 graves, although only about 1,200 are marked. Priests and their families who died while in Wilmington are buried under the church's altar.
By the mid-1800s, the congregation of Old Swedes had outgrown the building. The congregation would eventually build eight other churches, including what is now Trinity Episcopal Church in Wilmington. Though the church was originally a Swedish Lutheran church, voted to change the church's affiliation in 1845, becoming an Episcopal church when they could no longer find Swedish Lutheran priests after the last one departed in 1791.
The church building was declared a National Historic Landmark in 1961 and was added to the National Register of Historic Places in 1966.