Final answer:
The Mississippi River is the large river in the US that flows South and empties into the Gulf of Mexico, being one of the world's largest rivers.
Step-by-step explanation:
The large river in the United States that flows South and empties into the Gulf of Mexico is the Mississippi River. The Mississippi River is one of the largest rivers in the world and is a key geographic feature in North America. It travels from its northern source all the way to the southern United States, passing through several states before its waters reach the Gulf of Mexico.
The river has historical significance and has played an important role in commerce and transportation, particularly before the advent of the railway and highway systems. With its extensive drainage basin, the Mississippi River is crucial for agriculture, industry, and ecosystem diversity in the region.