[4] Margaret Renkl has written about the delta and its vulnerability to coal ash pollution from the James M. Barry Electric Generating Plant upstream along the Mobile River.

By the end of the last major ice age (approximately 18,000 years ago), when the sea level was much lower and Alabama's coastline was about 60 miles (97 km) south of its present location, the waterways of the delta valley extended much farther than their current-day southern termination at the head of Mobile Bay.

During the Mississippian period, people of the Pensacola culture built earthen mounds along Bottle Creek and the Tensaw River.

The schooner Clotilda arrived in the Delta on July 7, 1860, carrying 103 enslaved West Africans captured in Dahomey, and was scuttled to prevent being prosecuted under the Act Prohibiting Importation of Slaves.

[8] The last important battle of the American Civil War took place at the fortified town of Blakeley, located on the edge of the delta.

[10] The Mobile–Tensaw River Delta and the adjacent Mobile estuary make up one of the largest wetland ecosystems in the United States, which is why protecting its wide range of biodiversity is a top priority for conservators.

The Alabama Department of Conservation and Natural Resources (ADCNR) Game & Fish Division has also listed the Mobile-Tensaw Delta as one of their highest priorities for inclusion into the state Wildlife Management Area System.

[11] The delta is one of 327 watersheds (of the 2,100 in the United States) to be deemed as being of irreplaceable value to conserving populations of all freshwater fish and mussel species at risk.

[14] It is important to recognize that human activates resulting in upstream pollution within the Mobile River Basin have profound impacts on the Mobile-Tensaw Delta.

Dams distort the natural hydrological flow by either physically restricting movement of wildlife or by creating large areas of inhospitable habitat.

Both invasive plants and animals pose a threat to the native populations of wildlife that call the Mobile Delta home.

They are detrimental to the entire Alabama ecosystem because they will eat almost any type of plant or animal materials, including agricultural crops, food discarded by humans, carrion, small mammals, birds, turtles, snakes, and amphibians.