Profound social, economic, and environmental changes that include new land management practices are often associated with advancing agricultural frontiers. We argue that existing approaches to case studies do not allow for clear generalization or the systematic testing of hypotheses. As an alternative, our study uses Mill's method of agreement approach to synthesize results from seven long-term case studies of land cover change in frontier areas. We identify a number of generalizations that hold across the specific case studies. We also identify changes in the spatial organization of land use in agricultural frontier areas, which are typically characterized by agricultural expansion, growing population, and transportation improvements. We then evaluate the methodological strengths and weaknesses of Mill's method of agreement based on use in this study. Finally, we argue that agent-based models, using virtual landscapes and the logic of demographic standardization, are an important next step to facilitate methodologically defensible comparisons across case studies.