Probably from the practice in the U.S., prior to the American Civil War, of trading in slaves who were transported via the Mississippi River:
:* 1885, Mark Twain, Huckleberry Finn, ch. 42:
:*: "[H]e ain't no slave. . . . Old Miss Watson died two months ago, and she was ashamed she ever was going to sell him down the river, and said so; and she set him free in her will."
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