Increased sedimentation and nutrient cycle changes in Prairie Pothole Region wetlands associated with agriculture threaten the permanence and ecological functionality of these important resources. To determine the effects of land use on sedimentation and nutrient cycling, soil cores were analyzed for cesium-137 (137Cs), lead-210 (210Pb), and potassium-40 (40K) activities; textural composition; organic and inorganic carbon (C); and total nitrogen (N) from twelve wetlands surrounded by cropland, Conservation Reserve Program (CRP) lands, or native prairie uplands. Separate soil cores from nine of these wetlands were also analyzed for phosphorus (P), nitrate (NO3), and ammonium (NH4) concentrations. Wetlands surrounded by cropland had significantly greater linear sediment accretion rates than wetlands surrounded by CRP or native prairie. Linear sediment accretion rates from wetlands surrounded by cropland were 2.7 and 6 times greater than wetlands surrounded by native prairie when calculated from the initial and peak occurrence of 137Cs, respectively, and 0.15 cm y−1 (0.06 in yr−1) greater when calculated from 210Pb. Relative to wetlands surrounded by CRP, linear sediment accretion rates for wetlands surrounded by cropland were 4.4 times greater when calculated from the peak occurrence of 137Cs. No significant differences existed between the linear sediment accretion rates between wetlands surrounded by native prairie or CRP uplands. Wetlands surrounded by cropland had increased clay, P, NO3, and NH4, and decreased total C and N concentrations compared to wetlands surrounded by native prairie. Wetlands surrounded by CRP had the lowest P and NO3 concentrations and had clay, NH4, C, and N concentrations between those of cropland and native prairie wetlands. We documented increased linear sediment accretion rates and changes in the textural and chemical properties of sediments in wetlands with cultivated uplands relative to wetlands with native prairie uplands. These findings demonstrate the value of the CRP at protecting wetland catchments to reduce sedimentation.