The Calcasieu River (KAL-kuh-shoo) is a river on the Gulf Coast of southwestern Louisiana in the United States. Approximately 200 mi (320 km) long, it drains a largely rural area of forests and bayou country, meandering southward to the Gulf of Mexico. The name "Calcasieu" comes from the Native American Atakapa katkosh, for Eagle, and yok, to cry.

The Calcasieu rises in Vernon Parish, north of Leesville and flows initially southeast, passing through the Kisatchie National Forest southwest of Alexandria. It then turns southwest, flowing past Oakdale and Lake Charles, the largest city on the river. It enters the north end of the brackish Calcasieu Lake, an estuary on the Gulf of Mexico approximately 10 mi (16 km) southwest of Lake Charles. The lake is connected by a 5 mi (8 km) channel to the gulf on the south end. The lower portion of the river south of Lake Charles is paralleled by a navigable canal that connects to the Intercoastal Waterway.

In the early 19th century, the area of present-day Louisiana and Texas west of the Calcasieu and east of the Mexico. The dispute arose from differing interpretations of the Adams-Onis Treaty. The area became known as Neutral Ground and became a haven for privateers outside the legal jurisdiction of both nations.

Because the river passes through areas intensive in petroleum refining and other industries, petrochemical wastes have been found contaminating the river and estuarine environment along the lower Calcasieu river.