The area includes parts of the municipalities of Isla Mayor, Los Palacios y Villafranca, La Puebla del Río, Utrera, Las Cabezas de San Juan and Lebrija.

Approximately two millennia ago the wetlands comprised a large lagoon and estuary, known as Lacus Ligustinus [es] in Latin, leading to the Guadalquivir River mouth with some sand bars to the South.

[1] This silt has formed into a barrier of dunes extending approximately 70 kilometres (43 mi) along the coast, known as Arenas Gordas (English: "the fat sands").

[3] In the early 21st century, the Guadalquivir wetland region's main economic activity is agriculture, specialising in the cultivation of rice.

The National Park was established in 1969 as a nature reserve when the World Wildlife Fund joined forces with the Spanish Government to purchase a substantial part of the local wetlands in order to preserve them.