Sediment accumulation threatens the viability and hydrologic functioning of many naturally formed depressional wetlands across the interior regions of North America. These wetlands provide many ecosystem services and vital habitats for diverse plant and animal communities. Climate change may further impact sediment accumulation rates in the context of current land use patterns. We estimated sediment accretion in wetlands within a region renowned for its large populations of breeding waterfowl and migrant shorebirds and examined the relative roles of precipitation and land use context in the sedimentation process. We modeled rates of sediment accumulation from 1971 through 2100 using the Revised Universal Soil Loss Equation (RUSLE) with a sediment delivery ratio and the Unit Stream Power Erosion Deposition model (USPED). These models predicted that by 2100, 21–33 % of wetlands filled completely with sediment and 27–46 % filled by half with sediments; estimates are consistent with measured sediment accumulation rates in the region reported by empirical studies. Sediment accumulation rates were strongly influenced by size of the catchment, greater coverage of tilled landscape within the catchment, and steeper slopes. Conservation efforts that incorporate the relative risk of infilling of wetlands with sediments, thus emphasizing areas of high topographic relief and large watersheds, may benefit wetland-dependent biota.