The Missouri is the longest river that flows from north to south in the U.S.; however, it does initially flow north a bit before turning southeast. The next two longest north-to-south rivers are the Mississippi and the Colorado.
The Missouri begins in Montana and flows north and to the east through Missouri before turning south in North Dakota; it is 2,500 miles long. The Mississippi flows south from Minnesota to New Orleans and is 2,339 miles long. The Colorado flows from the Rocky Mountains to Baja, California and is 1,450 miles long. If the Missouri is excluded for initially flowing north and east, the next longest river would be the Atchafalaya at 1,420 miles.