This paper presents the first assessment of the Uummannaq ice stream system (UISS) in West Greenland. The UISS drained ~6% of the Greenland ice sheet (GrIS) at the Last Glacial Maximum (LGM). The onset of the UISS is a function of a convergent network of fjords which feed a geologically controlled trough system running offshore to the shelf break. Mapping, cosmogenic radiogenic nuclide (CRN) dating, and model output reveal that glacially scoured surfaces up to 1266 m above sea level (asl) in fjord-head areas were produced by warm-based ice moving offshore during the LGM, with the elevation of warm-based ice dropping westwards to ~700 m asl as the ice stream trunk zone developed. Marginal plateaux with allochthonous blockfields suggest that warm-based ice produced till and erratics up to ~1200 m asl, but CRN ages and weathering pits suggest this was pre-LGM, with only cold-based ice operating during the LGM. Deglaciation began on the outer shelf at ~14.8 cal. kyrs B.P., with Ubekendt Ejland becoming ice free at ~12.4 ka. The UISS then collapsed with over 100 km of retreat by ~11.4 ka–10.8 cal. kyrs B.P., a rapid and complex response to bathymetric deepening, trough widening, and sea-level rise coinciding with rapidly increasing air temperatures and solar radiation, but which occurred prior to ocean warming at ~8.4 cal. kyrs B.P. Local fjord constriction temporarily stabilized the unzipped UISS margins at the start of the Holocene before ice retreat inland of the current margin at ~8.7 ka.