In semiarid and sub-humid Saskatchewan, Canada, there is growing interest in draining depressional areas within the landscape (prairie potholes) despite a clear understanding of the potential nutrient loss to nearby water sources. Nutrient fate and form can vary greatly depending on soil moisture regime; the aim of this study was to determine how drainage duration affects the nitrogen (N) and phosphorus (P) availability and mobility under varying moisture levels. A greenhouse experiment was conducted using four depressional soils from south-eastern Saskatchewan, which had been drained for 0, 14, 20, and 42 yr, and one undrained midslope soil for comparison. The potted soils were seeded with wheat (Triticum aestivum L.), three different moisture scenarios applied, and leachate was collected weekly. Drained soils had greater aboveground biomass and N and P plant uptake compared with undrained soil. These differences were most pronounced in the 20 yr drained soil, which had a 30% increase in growth, 45% greater N uptake, and 62% greater P uptake than the undrained soil. Nitrogen mineralization and water holding capacity appeared to affect nutrient losses. The soil that contributed the most to nutrient losses varied under different moisture scenarios; low water holding capacity contributed to nutrient leaching under lower moisture scenarios, whereas enhanced mineralization increased losses under above-average moisture.