This paper discusses the response of topography and river networks to non-uniform lithology and tectonic forcing in the Umbria-Marche sector of the Apennines fold and thrust belt. We ruled out the role of variable erosion of rock types and interpret channel steepness data in terms of rock uplift, discovering a southward increase in the total amount of uplift. Such a trend appears as the large-scale response to uneven vertical motions of different sectors of the mountain ridge and foothills. The general coincidence between sector boundaries and transversal, NE-SW striking faults mapped by seismic interpretation in the outer zone of the fold and thrust belt, suggests that such faults extend to the SW, beneath the allochthonous thrust sheets of the mountainous area. Therefore, it may be inferred that such transversal faults represent long-lived, deeply rooted basement structures compartmentalizing both the axial and the outer zones of the fold and thrust belt. We suggest that differential uplift was essentially controlled by variable amounts of basement thrust displacement characterizing the compartmentalized belt. This interpretation deviates from a more conventional view that uplift of the central Apennines, particularly prominent in the south, is dynamically supported. Our results, besides shedding new light into the active tectonic behavior of a large portion of the Italian peninsula, also provide general insights into the surface response to the differential behavior of crustal blocks produced by along-strike segmentation of active mountain belts.