Some of the deepest themes of the book, those of slavery and the inability of people to avoid judging and categorizing others are certainly understandible without a deep history of the American nation. What changes, if the book is read with a knowledge of these things, are some of the more specific aspects of both Jim's quest for freedom and the interactions between and among the various characters.
There are so many interesting questions that can be asked that become more interesting still with an understanding of the history of the country, and the forces changing things in that moment. The country was about to be swept by the idea of compulsory education, and Huck is in some ways a model of what can be accomplished (in terms of educating oneself) with hard work, curiosity and an inclination to get into stick situations. This can become even more nuanced with an understanding of Twain's views on education.
These kinds of things go throughout the book. I can echo the previous post in that the understanding isn't necessary to enjoy the story, but it can certainly add some interesting levels to discussions of the book, the characters, and Twain's own attitudes that are evident in his writing.