The two crossword solutions for the term 'Major U.S. River' are Ohio (4 letters) and Missouri (8 letters). The Ohio River is a 981-mile long river that flows through six states in the United States, including Ohio, Pennsylvania, West Virginia, Kentucky, Indiana, and Illinois. It is the largest tributary of the Mississippi River and is the second-largest river in the United States. The Missouri River is the longest river in North America, stretching 2, 341 miles from its source in the Rocky Mountains of Montana to its confluence with the Mississippi River near St. Louis, Missouri. It is the primary drainage system for the central United States, draining an area of more than 500, 000 square miles.