I read somewhere that the mathematician John von Neumann drove across the country over twenty times in the late 40s and early 50s -- between Princeton and Los Alamos, I would guess. I also read that in the late 40s some of Norbert Wiener's grad students drove from Boston to Mexico City for a cybernetics conference --- they were gone for months!
Earlier, in the 1930s, there was the migration of Oakies from the dust bowl to California, as described in The Grapes of Wrath, which, come to think of it, is another road novel.
In 1957 my family, a young couple with two little kids, moved from Wisconsin to Seattle, driving in our Plymouth station wagon, camping along the way. I was very young but I recall stopping for a flash flood, and another time we had to stop for a cattle drive that was crossing the highway, driven by actual cowboys on horseback! I remember it as one of the great adventures of my life.