We used facies analysis to reconstruct the Pleistocene sedimentary evolution of seven cores from the central-northern Po Plain, Italy. The cores record an overall regressive sequence consisting of shallow-water marine and fluvial-deltaic deposits overlain by fully continental sediments. We used magneto-stratigraphy to date marine and fluvial-deltaic sediments to the early Pleistocene and continental sediments to the middle–late Pleistocene. Sediment accumulation rates were ∼30–40 cm/k.y. in the early Pleistocene, whereas relevant unconformities and/or an overall reduction in sediment accumulation rates characterized the middle–late Pleistocene. A simple Airy compensation model was applied to restore actual sediments elevations to elevations at times of deposition expressed in meters above current sea level. The correlation of isostatically corrected sedimentary facies to a sea-level curve obtained from classic oxygen-isotope studies shows that an event of rock uplift on the order of ∼70–120 m occurred in the middle–late Pleistocene. Literature studies of vegetational cyclicity, used in conjunction with the sea-level curve, allowed us to link sedimentary facies to climate variability. We propose that the onset of fully and persistently continental sedimentation occurred in response to the waxing of the first major Pleistocene glaciation in the Alps, currently correlated to marine isotope stage 22 at ca. 0.87 Ma, and that the episode of uplift occurred (at least in part) as a consequence of erosion and crustal rebound of the Alpine chain triggered by Pleistocene glacial-interglacial cycles.