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The High Plains Aquifer (HPA), underlying parts of 8 states from South Dakota to Texas, is one of the largest fresh water aquifers in the world and accounts for 30% of the groundwater used for irrigation in the US. Determining the distribution of HPA’s hydraulic conductivity (K) is critical for water management and addressing water quality issues. K is traditionally estimated from well pumping data coupled with computer modeling and is known to be highly variable, spanning several orders of magnitude for the same type of rock. Here we show that applying our innovative method of determining effective horizontal K to HPA (based on surface drainage patterns and a dynamic equilibrium assumption) produced results generally consistent with those from traditional methods but reveals much more detailed spatial variation. With the exception of a few places such as the Sand Hills area, our results also show for the first time (to the best of our knowledge) a distinct relationship between surface stream drainage density and subsurface aquifer K in a major aquifer system on a regional scale. Because aquifer particle size strongly controls K, our results can be used to study patterns of past sediment movement and deposition.