In the final confrontation with Jefferson, Clark picks up a piece of wood with his left hand. When it cuts to a wide shot, however, he is holding it in his right.
A map seen early in the film shows Lewis and Clark beginning their expedition in Charlottesville, Virginia. In fact, they departed from St. Louis, Missouri.
Though the film depicts Lewis and Clark as the sole explorers on the expedition, they were actually accompanied by over 30 people.
Throughout the film, Clark references a deceased wife named Emily and Lewis writes letters back home to his fiancee Abigail. In reality, Lewis was not engaged at the time and indeed never married (though the idea of a long-distance correspondence with someone named Abigail may have been inspired by the real-life letters written between John and Abigail Adams). On the other hand, though Clark's dead wife is a fiction, at the time of the expedition he actually was engaged to a girl named Julia Hancock whom he promptly married upon his return. She died years later and Clark subsequently married her cousin Harriet Radford.
At one point in the story, Eagle tells Jefferson that he is being put on the two-dollar bill. In reality, the two-dollar bill was not created until 1862 and it originally featured Alexander Hamilton. Jefferson didn't replace him until 1869.
Eagle is told near the end of the film that he will be known as the great symbol of this new nation. In truth, the bald eagle had already been adopted by Congress as the national bird, and placed on the official seal, in 1782.