The Pocomoke Sound and Maryland Marine Properties Wildlife Management Areas lie on the north side of the Sound; the Saxis Wildlife Management Area on the east.

In 1635 the Sound was the scene of the first recorded naval battle in North America between Englishmen.

The dispute was between the Virginia Company and Lord Baltimore, the proprietor of the Maryland Colony and William Claiborne over the rights to Kent Island.

In 1785, after years of disputes over fishing in the Sound and on the Pocomoke River, Maryland and Virginia entered into an interstate compact that regulated fishing in the area, established a common and free waterway, and covered how criminal trials concerning each other's citizens should be handled.

[3] In Wharton v. Wise, 153 U.S. 155 (1894), the Supreme Court of the United States determined that Pocomoke Sound was not covered by this famous interstate compact.