Historically and in present times, the John Day basin has never had a large human population. Most archaeological evidence points to this area being used seasonally, most likely when fish such as steelhead were running in the river.
In the mid-1800's homesteaders started moving into the area to ranch. Many tried their fortunes and succeeded (or some failed) to varying levels. Until the middle of the twentieth century, sheep and cattle ranches were equally common, but as the market for wool has declined after World War II, cattle ranching has come to dominate in the area.
John Day Fossil Beds National Monument doesn't just contain fossils, but also places where traces of the people who have lived here, past and present. Look for ghost towns or abandoned places, slowing being reclaimed by the Earth, on your way to the monument.