While large earthquakes have been documented in stable continental regions, such as the central United States, they occur too infrequently to provide reliable observations of earthquake-related impacts. Using the state of Indiana as a case study, we investigate the impacts of five deterministic scenarios—three occurring outside the borders of the state and two within the state. They include a M7.3 Wabash Valley event in southern Illinois, a M7.6 New Madrid event in southeastern Missouri, a M6.2 event in west central Ohio, a M6.2 event near Evansville, Indiana, and a M5.8 Indianapolis event. The locations and magnitudes are based on known fault locations and credible interpretations of the earthquake history in the region. We use a combination of the US Geological Survey’s ShakeMap and the Federal Emergency Management Agency’s (FEMA) Hazus software packages to assess earthquake-triggered ground shaking and its effects on the built environment. We also use the United States Geological Survey (USGS) Ground Failure estimation tool to examine the spatial distribution of anticipated earthquake-induced landslides and liquefaction. The five main deterministic scenario models indicate that moderate-sized urban earthquakes may represent a greater threat to a state like Indiana than a large-magnitude event from the New Madrid seismic zone. To better understand the influence of earthquake source parameters on impacts, we conducted a sensitivity analysis for earthquakes near Indianapolis and Evansville, where we reviewed losses due to differences in magnitude, depth, strike, and dip. Based on the model projections, magnitude and depth have first-order and relatively predictable influence on losses. The orientation and dip of the causative fault in relation to populated areas can alter economic losses for an event of the same magnitude by 13%–32%. Deterministic scenario analyses, such as those presented here, can potentially be of widespread utility for understanding earthquake impacts in the central United States and other low-seismicity, stable continental regions.