The Late Glacial (14 700–11 700 cal BP) is a key climate period marked by rapid but contrasted changes in the Northern Hemisphere. Indeed, regional climate differences have been evidenced during the Late Glacial in Europe and the northern Mediterranean. However, past climate patterns are still debated since temperature and precipitation changes are poorly investigated towards the lower European latitudes. Lake Matese in southern Italy is a key site in the central Mediterranean to investigate climate patterns during the Late Glacial. This study aims to reconstruct climate changes and their impacts at Matese using a multi-proxy approach including magnetic susceptibility, geochemistry (XRF core scanning), pollen data and molecular biomarkers like branched glycerol dialkyl glycerol tetraethers (brGDGTs). Paleotemperatures and paleo-precipitation patterns are quantitatively inferred from pollen assemblages (multi-method approach: modern analogue technique, weighted averaging partial least-squares regression, random forest and boosted regression trees) and brGDGT calibrations. The results are compared to a latitudinal selection of regional climate reconstructions in Italy to better understand climate processes in Europe and in the circum-Mediterranean region. A warm Bølling–Allerød and a marked cold Younger Dryas are revealed in all climate reconstructions inferred from various proxies (chironomids, ostracods, speleothems, pollen, brGDGTs), showing no latitudinal differences in terms of temperatures across Italy. During the Bølling–Allerød, no significant changes in terms of precipitation are recorded; however, a contrasted pattern is visible during the Younger Dryas. Slightly wetter conditions are recorded south of 42∘ N, whereas dry conditions are recorded north of 42∘ N. During the Younger Dryas, cold conditions can be attributed to the southward position of North Atlantic sea ice and of the polar frontal jet stream, whereas the increase in precipitation in southern Italy seems to be linked to relocation of Atlantic storm tracks into the Mediterranean, induced by the Fennoscandian ice sheet and the North European Plain. By contrast, warm conditions during the Bølling–Allerød can be linked to the northward position of North Atlantic sea ice and of the polar frontal jet stream.