Denman Glacier, East Antarctica, holds an ice volume equivalent to a 1.5 m rise in global sea level. Using satellite radar interferometry from the COSMO-SkyMed constellation, we detect a 5.4 ± 0.3 km grounding line retreat between 1996 and 2017-2018. A novel reconstruction of the glacier bed topography indicates that the retreat proceeds on the western flank along a previously unknown 5 km wide, 1,800 m deep trough, deepening to 3,400 m below sea level. On the eastern flank, the grounding line is stabilized by a 10 km wide ridge. At tidal frequencies, the grounding line extends over a several kilometer-wide grounding zone, enabling warm ocean water to melt ice at critical locations for glacier stability. If warm, modified Circumpolar Deep Water reaches the sub-ice-shelf cavity and continues to melt ice at a rate exceeding balance conditions, the potential exists for Denman Glacier to retreat irreversibly into the deepest, marine-based basin in Antarctica.