Large river floods are a key water source for many lakes in fluvial periglacial settings. Where permeable sediments occur, the distribution of permafrost may play an important role in the routing of floodwaters across a floodplain. This relationship is explored for lakes in the discontinuous permafrost of Yukon Flats, interior Alaska, using an analysis that integrates satellite-derived gradients in water surface elevation, knowledge of hydrogeology, and hydrologic modeling. We observed gradients in water surface elevation between neighboring lakes ranging from 0.001 to 0.004. These high gradients, despite a ubiquitous layer of continuous shallow gravel across the flats, are consistent with limited groundwater flow across lake basins resulting from the presence of permafrost. Permafrost impedes the propagation of floodwaters in the shallow subsurface and constrains transmission to “fill-and-spill” over topographic depressions (surface sills), as we observed for the Twelvemile-Buddy Lake pair following a May 2013 ice-jam flood on the Yukon River. Model results indicate that permafrost table deepening of 1–11 m in gravel, depending on watershed geometry and subsurface properties, could shift important routing of floodwater to lakes from overland flow (fill-and-spill) to shallow groundwater flow (“fill-and-seep”). Such a shift is possible in the next several hundred years of ground surface warming, and may bring about more synchronous water level changes between neighboring lakes following large flood events. This relationship offers a potentially useful tool, well-suited to remote sensing, for identifying long-term changes in shallow groundwater flow resulting from thawing of permafrost.