We relate the historical (1850-2000) spatial and temporal changes in cropland cover in the conterminous United States to several socio-economic and biophysical determinants using an eco-region based spatial framework. Results show population density as a major determinant during the nineteenth century, and biophysical suitability as the major determinant during the twentieth century. We further examine the role of technological innovations, socio-economic and socio-ecological feedbacks that have either sustained or altered the cropland trajectories in different eco-regions. The cropland trajectories for each of the 84 level-III eco-regions were analyzed using a nonlinear bi-analytical model. In the Eastern United States, low biophysically suitable eco-regions, e.g., New England, have shown continual decline in the cropland after reaching peak levels. The cropland trajectories in high biophysically suitable regions, e.g., Corn Belt, have stabilized after reaching peak levels. In the Western United States, low-intensity crop cover (<10 %) is sustained with irrigation support. A slower rate of land conversion was found in the industrial period. Significant effect of Conservation Reserve Program on planted crop area is found in last two decades (1990-2010).