English settlers first moved to what would become Mardela Springs in 1664, drawn by good farmland, natural springs, and Barren Creek, a tidal waterway draining into the Nanticoke River. Tobacco farmers brought their crops, bound for export, to a tobacco inspection warehouse there as early as 1704, and several grist and saw mills were built along the creek. By the late 1700s, a hotel had been built near the natural springs, a convenient stopover for travelers on the main road from the north to Quantico and Princess Anne.

The springs became a great tourist attraction in the 1840-1890 period; visitors from Philadelphia, Baltimore, Washington, and Richmond came to “take the waters.” In the latter part of the 19th century, enterprising townsmen began bottling the water and shipping it to points up and down the mid-Atlantic coast. The town had gone through several names by then, but in 1893 it finally settled on Mardela (Maryland/Delaware) Springs.

Farms in the area were mostly small and family-run. Even in the mid 1800s, only one in five households owned slaves; a large settlement of free blacks lived nearby. Other businesses came, including shipbuilding, fruit and vegetable canning, and, in 1890, the railroad. But by the mid 1900s, the tourism and commercial bustle had essentially died. The hotel had burned down long ago; the bottled-water company had closed, the trains stopped coming, and most residents found jobs in nearby Salisbury or in Seaford, Delaware. Mardela Springs turned into a pleasant “bedroom” community.