Lewis & Clark certainly don't belong on this list, though . . . their expedition may have made for some interesting discussion, but in retrospect is was one of the more inconsequential stories in American history.
Lewis and Clark could just as well have been Lewis and Martin........Jefferson had to send somebody.............
The Corps of Discovery opened up the interior of the US trans-Mississippi area, especially the north and northwest to land based exploration and settlement. It would have happened sooner or later, but a delay of 10 years in this process would probably have left the Pacific northwest as part of Canada, and could have left the California Gold Rush as occurring in Mexican California. It is possible that the Mexican territory in the southwest, including California, might have never have become American, without a much more violent struggle!