The Wye River is a 16.3-mile-long (26.2 km)[1] tributary of the Chesapeake Bay, on the Eastern Shore of Maryland.

The river is popular with recreational boaters because of its secluded anchorages, fishing, crabbing and proximity to the tourist attractions of St. Michaels, Maryland.

The river's features include the 2,800-acre (11 km2) Wye Island, most of which is part of the Wye Island Natural Resources Management Area, managed by the Maryland Department of Natural Resources State Forest and Park Service.

William Paca, the third governor of Maryland and a signatory to the Declaration of Independence, once owned the island.

They conduct agricultural research and education, in cooperation with the nearby Aspen Institute Wye River Conference Centers.