The Aransas people left the area approximately 700 years ago, and were replaced around 1400 CE[1] by the Copane Indians, for whom the bay is named.

[3] Cabeza de Vaca is thought to have been the first European to sight the bay in the early 16th century, evidenced by the descriptions in his logs that match the detail of the area.

The port later served as a strategically important locale during the Texas Revolution and the American Civil War, and was the site of a settlement that is now completely abandoned.

[5] The town of St. Mary's of Aransas was founded southwest of Copano and thrived as a port and wood mart, until numerous shipwrecks caused by the bay's hidden reefs concluded its use in 1875.

Bayside developers aimed to attract fruit and vegetable growers to the plots made available and advertised nationwide, but large amounts of land were purchased by speculators, raising demand and forcing further annexation.

[12] The bay's maximum depth is 3 metres (9.8 ft),[13] and in contrast to the Laguna Madre (approximately 80 miles down the coast to the south), is not hypersaline.

At both mouths, marshes covering several square miles stretch from the confluences with Copano Bay and forming several saline lakes.

[13] The reefs provide habitat for fish and sustenance for a wide variety of birds including the black-bellied whistling-duck, black-necked stilt, brown pelican, gull-billed tern, reddish egret, roseate spoonbill, seaside sparrow, white-faced ibis and the whooping crane.

[13] In 2003, the United States Department of the Interior granted $574,000 to Texas Parks and Wildlife to purchase over 900 acres (3.6 km2) of prime birding habitat at Egery Flats and the mouth of the Aransas River, to prevent further development.

[12] In 1997, a pipeline owned by Koch Industries burst in the marsh in Refugio County, two miles (3 km) west of Copano Bay near the Aransas River, spilling 1,000 gallons of oil over a 10-acre (40,000 m2) area.