In 1791 the Spaniard José María Narváez explored and named Padilla Bay, calling it Seno Padillo, in honor of Juan Vicente de Güemes Padilla Horcasitas, the viceroy of New Spain.

Part of the estuary tidal flats are contained by dikes built in order to make farmland out of the mudflats.

The Swinomish Channel is a salt-water channel in Washington State, United States, which connects Skagit Bay, to the south, and Padilla Bay, to the north, separating Fidalgo Island from mainland Skagit County.

The Padilla Bay National Estuarine Research Reserve is an area of 8,004 acres (32 km2) of estuary located in Skagit County.

The reserve contains the Breazeale Interpretive Center, which features exhibits about the natural history and ecology of the estuary and bay, fish tanks, a hands-on room and a video theater.