The thought of your ancestors of 100 or 200 years ago traveling along a modern-day interstate highway may seem amusing as interstate highways didn’t exist until the 1950s. Yet, it is quite possible that your ancestors traveled along the same routes as today’s interstates, plus or minus a very few miles.
Westward migration in the United States usually took place in the path of least resistance: on riverboats where practical or on pathways along rivers when boat travel was not available. In cases where there was no river to follow, overland travel generally went along the path of least resistance, too: through valleys, through mountain passes, and perhaps straight across the flatlands and prairies.
When studying migration patterns throughout history in the United States, we can see hundreds of examples. In New England, the first inland areas to be settled were along the Merrimack River, the Connecticut River, the Penobscot River, and the others.