Although sporadic and infrequent, flooding events in ephemeral watersheds are a critical component to the water, sediment and biogeochemical cycles in arid and semiarid regions. In the Southwestern United States, intense thunderstorms during the summer monsoon season interact with landscapes characterized by topographic complexity and soils of low infiltration capacity to produce large magnitude floods and flash floods. In this study, we examine the hydrometeorological conditions and hydrologic response of an extreme monsoon flood event in the Río Puerco watershed of north-central New Mexico and its downstream effects in the Río Grande, a major continental-scale river basin. The summer storm in early September 4-11, 2003 generated flash flooding in headwater basins and river flooding extending through the semiarid basin and downstream into the Río Grande for several tens of kilometers. We characterize the hydrometeorological conditions prior to the flood event using precipitation estimates from rain gauge records, NEXRAD radar data, and synoptic weather conditions over the 18,000 km2 Río Puerco basin. Then, we present the spatial and temporal variability in hydrologic response based on a set of nested stream gauges in river channels and irrigation canals as well as a network of instrumented well transects installed along the Río Grande. Our analysis illustrates the propagation, dampening, and attenuation of a large monsoonal storm through a semiarid ephemeral tributary into a regional river system from both a surface and groundwater hydrology perspective. By estimating the frequency of the rainfall and flood event in the system relative to the historical record and known shifts in climate regime, we discuss the importance of extreme flood events in semiarid tributary systems and their downstream effects in large regional river basins.