The Mississippi Gulf Coast, also known as Mississippi Coast, Mississippi Gulf Coast region, Coastal Mississippi, and The Coast, is the area of Mississippi along the Mississippi Sound at the northern extreme of the Gulf of Mexico.

At the state's creation, Hancock and Jackson were the only two counties to make up this region. However, before the end of the first centennial, subdivisions in the counties led to the formation of Harrison County, as well as the pineywoods counties of Pearl River, Stone and George.

The Mississippi Gulf Coast consists of many cities that lie directly on the Mississippi Sound. The U. S. Census Bureau divided the Metropolitan Statistical Area (MSA) for the Mississippi Gulf Coast in 2003, which previously consisted of the three coastal counties (Hancock; Harrison; Jackson), into two MSAs that included two additional counties (George; Stone). Cities in the new Metropolitan Statistical Area include the original French settlements Biloxi and Ocean Springs, as well as Waveland, Bay St. Louis, Diamondhead, Pass Christian, Long Beach, Gulfport, D'Iberville, Gautier, Pascagoula, Moss Point, Lucedale, and Wiggins.

The Biloxi people lived in the region at least as early as 1699.

In 1699, Pierre Le Moyne d'Iberville arrived to establish a colony near the mouth of the Mississippi River. He landed on the Ship Island, and three days later, arrived on the Mississippi Gulf Coast, establishing a colony and building Fort Maurepas, which served as the first capital of French Louisiana. The fort became a base of operations to continue exploring the area.

The French settlers found the area to be difficult to maintain a settlement. According to Bunn & Williams (2007), factors such as death of crops, lack of fresh water, lack of discipline, and illness led to difficulty in maintaining the colonization of the area. Furthermore, due to political concerns, the capital of French Louisiana was moved to Mobile in 1701; the fort was abandoned by 1702. Despite a temporary move of the capital to Biloxi during the construction of New Orleans, previous failures kept the area from playing a further role in French colonization efforts in the region.

When Mississippi entered the Union in 1817, the majority of the population lived in Northern parts of the state. At statehood, the population of the coast comprised 2.5% of the state's total. Likewise, the Census lists only 586 of the state's 30,061 slaves as living on the Mississippi Gulf Coast. After statehood, the coastal regions remained a frontier, with cultural influences coming from the Mediterranean area. According to Kenneth P'Pool, deputy historic preservation officer at MDAH, "The Coast's situation along ... the Gulf of Mexico — both facilitated the region's ethnic diversity and maintained its ties to the rest of the world much more easily than was possible for other regions of [Mississippi]."

Fort Massachusetts, on Ship Island, was seized during the American Civil War.