If you'd sailed here in 1519 with Spanish explorer Alonzo Alvarez de Pineda you might have gazed in wonder at the vast coastal prairies and brush covering three million acres, an area four times the size of Rhode Island. The Spanish returned to settle the region more than two hundred years later in 1749. Colonists brought cattle and cleared the brushlands —displacing the Coahuiltecan Indians and other native tribes, as well as wildlife. The Spanish left lasting cultural influence in the descendents, architecture, customs and place names. After the U.S. annexed Texas in 1845, clearing lands for agriculture continued and accelerated with twentieth century mechanization.

As early as the late 1800s, conservationists identified the Laguna Madre as important for waterfowl. By the 1930s, efforts were underway to designate a National Wildlife Refuge. But in 1941 priorities shifted to World War II. The War Department acquired lands on the mainland and South Padre Island for aerial gunning and bombing ranges. Meanwhile, the U.S. Fish and Wildlife Service in 1941 advocated protection for the "large rafts of wintering redhead ducks that frequent this section of Laguna Madre" and for the dwindling thorn forests. In March of 1946, Congress established Laguna Atascosa NWR.