This paper takes its inspiration from Karl W. Butzer's course on the Human Use of Landforms at the University of Chicago. It builds upon that concept through an exploration of regional settlement patterns and landforms in the Deccan volcanic province of west-central India. The first section develops a conceptual framework for analyzing human adjustment to landforms on regional, settlement, and site scales. The second section employs that framework to analyze four major landform-settlement configurations in the Deccan from antiquity to the end of the eighteenth century. The Satavahana kingdom (ca. 100 BCE to 200 CE) had a strong southeast to northwest alignment along the Godavari River. Their capital city of Paithan was located at a navigable sacred ford across the river (tirtha), which was linked with upstream confluences (sangams), tanks (kunds), mountain passes (ghats), and port cities on the Arabian Sea. Subsequent Hindu dynasties (ca. 850–1300 CE) shifted from fluvial landforms to a north-south alignment along steep mesa escarpments and buttes in the central Deccan that provided defensive fortress and cave temple sites. Sultanate and Mughal forces expanded the urban footprint on nearby plateau lands at sites protected by surrounding mesas (ca. 1330–1700 CE). These cities were supported by local watershed runoff and long distance water channels. The final precolonial phase of Deccan settlement entailed a shift from the semiarid central plateaus to humid headwaters of the Western Ghats, whose buttes and scarps provided sites for scores of forts controlled by the founder of the Maratha empire Chhatrapati Shivaji in the seventeenth century. Maratha success led to development downstream at the capital city of Pune (1627–1803 CE), located at a river confluence flanked by mesas, which combined the strategies of previous periods. Over two millennia these four distinct, yet intersecting, patterns of human-landform relations have shaped an evolving geocultural region on the Deccan plateau that deserves comparison with other flood basalt regions.