Short rotation willow (SRW) is a land management strategy involving the cultivation of rapidly growing, biomass-rich herbaceous-woody plants. This practice holds promise for renewable energy production, water quality preservation, carbon sequestration, greenhouse gas (GHG) mitigation, enhancement of soil extracellular enzyme activities (EEAs), and promotion of overall soil health. The rapid growth of SRW demands substantial water and nutrient resources, posing concerns when cultivated in marginal riparian lands within the Prairie Pothole Region (PPR), potentially leading to alterations in groundwater table (GWT) depth fluctuations, elevated soil salinity levels, and disruptions to biogeochemical cycles. Hence, this study comprehensively evaluated the effects of establishing SRW as a degraded marginal riparian land use practice in the PPR and attempted to answer several vital questions in the field and microcosm scale on soil hydrology, salinity, nutrients, soil organic carbon (SOC), GHG emissions, and EEAs involved in biogeochemical cycling. In a field experiment, the effects of SRW were evaluated by measuring the depth to GWT, groundwater and soil electrical conductivity (EC), macronutrients (N, P, K, and S), and SOC content in different fractions and chemical compositions during the first rotation (3-year cycle) compared with adjacent annual crop and pasture in two semi-arid PPR sites. In a microcosm experiment, GHG (CO2, CH4, and N2O) emissions and EEAs [β-glucosidase (BG), N-acetyl glucosaminidase (NAG), and alkaline phosphatase (AP)] were measured in intact soil cores treated with declining water tables and different groundwater salinity levels. No consistent land use impacts on GWT or soil EC were observed between sites. Land use in site B significantly impacted GWT depth, implying site-specific factors, such as topography and soil characteristics, may be dominant over land use effects. Under SRW, the levels of macronutrients in the soil varied but did not significantly reduce the overall nutrient content of the soil. Total SOC was highest in pasture; light fraction organic carbon and particulate organic carbon followed a similar land use pattern, i.e., pasture > SRW = annual crop. Land uses affected GHG emissions significantly in the order of pasture > annual crop = SRW. GHG emission varied with salinity and GWT but there was no interaction with land use practices. Soil EEAs were significantly impacted by different land uses, i.e., pasture > annual crop = SRW, suggesting that the effects resulted from associated SOC. Our microcosm experiment suggests that the SRW land use practice holds promise as a sustainable Nature-Based Solution for enhancing climate resiliency in PPR. It exhibits a lower global warming potential compared to annual crop and pasture. Therefore, widespread implementation of the SRW land use practice in degraded marginal land could help mitigate the effects of climate change in the region.