Large-scale coupling between headwater catchments and downstream depocentres is a critical influence on long-term fluvial system behaviour and on the creation of the fluvial sedimentary record. However, it is often difficult to examine this control over multiple Quaternary glacial cycles and it has not been fully explored in karst basins. By investigating the Pleistocene glacial and fluvial records on and around Mount Orjen (1894 m) in Montenegro, we show how the changing connectivity between glaciated mountain headwater source zones and downstream alluvial basins is a key feature of long-term karst system behaviour – especially in relation to the creation and preservation of the surface sedimentary record. Middle and Late Pleistocene glacial deposits are well preserved on Mount Orjen. Uranium-series dating of 27 carbonate cements in fluvial sediments shows that many alluvial depocentres were completely filled with coarse glacial outwash before 350ka during the largest recorded glaciation. This major glaciation is correlated with the Skamnellian Stage in Greece and Marine Isotope Stage 12 (MIS 12, c 480–420ka). This was a period of profound landscape change in many glaciated catchments on the Balkan Peninsula. Later glaciations were much less extensive and sediment supply to fluvial systems was much diminished. The extreme base level falls of the Late Miocene produced the world's deepest karst networks around the Mediterranean. After MIS 12, the subterranean karst of Mount Orjen formed the dominant pathway for meltwater and sediment transfer so that the depositional basins below 1000 m became disconnected (uncoupled) from the glaciated headwaters. There is little evidence of post-MIS 12 aggradation or incision in these basins. This absence of later Pleistocene and Holocene fluvial activity means these basins contain some of the thickest and best-preserved outwash deposits in the Mediterranean. •We assess glacial–fluvial system coupling over multiple glacial cycles.•We analyse 12 alluvial records using 48 sedimentary exposures and 27 U-series ages.•MIS 12 was a period of profound landscape change and enhanced sediment supply.•Deep karst exerted a major control on Pleistocene glacial–fluvial processes.•Karst drainage is a major control on the preservation of the alluvial record.