To investigate the mechanism driving active extension in the central and southern Italian Apennines and the geography of seismic hazard, we compare spatial variations in upper crustal strain-rate measured across exposed fault scarps since 15 ± 3 ka with data on cumulative upper-crustal strain and topographic elevation, and free-air gravity, P-wave tomography and SKS splitting delay times that are a proxy for strain in the mantle. High extensional strain-rates across the Apennines since 15 ± 3 ka (0.4–3.1 mm/yr along 90 km transects) occur in two areas (Lazio-Abruzzo; SE Campania and Basilicata) where values for finite extensional strains that have developed since 2–3 Ma are highest (2–7 km cumulative throw), and where mean elevation in 5 × 90 km NE–SW boxes is > 600 m; the intervening area (NW Campania and Molise) with < 600 m mean elevation in 5 × 90 km boxes has extension-rates < 0.4 mm/yr and lower values for finite extensional strains (< 2 km cumulative throw). These two areas with high upper-crustal strain-rates overlie mantle that has relatively-long spatially-interpolated SKS delay times (1.2–1.8 s) indicating relatively-high mantle strains and free-air gravity values (140–160 mGals); the intervening area of lower extension-rate has shorter spatially-interpolated SKS delay times (0.8–1.2 s) and lower free-air gravity values (120 mGals). The two areas with high upper crustal strain-rates and strain, mean elevation, and mantle strain, coincide with the northern and southern edges of a slab window in the Tyrrhenian–Apennines subducting plate that has been inferred from published P-wave tomography. Together these correlations suggest that dynamic support of the topography by mantle flow through the slab window may control the present day upper crustal strain-rate field in the Apennines and the geography of seismic hazard in the region.