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This study evaluated the effects of plastic mulched ridge-furrow cropping on soil biochemical properties and maize (Zea mays L.) nutrient uptake in a semi-arid environment. Three treatments were evaluated from 2008 to 2010: no mulch (narrow ridges with crop seeded next to ridges), half mulch (as per no mulch, except narrow ridges were mulched), and full mulch (alternate narrow and wide ridges, all mulched with maize seeded in furrows). Compared to the no mulch treatment, full mulch increased maize grain yield by 50% in 2008 and 25% in 2010, but reduced yield by 21% in 2009 after low precipitation in early growth. Half mulch had a similar grain yield to no mulch in the three cropping years, suggesting half mulch is not an effective pattern for maize cropping in the area. Mulch treatments increased aboveground nitrogen (N) uptake by 21-34% and phosphorus (P) uptake by 21-42% in 2008, and by 16-32% and 14-29%, respectively, in 2010; but in 2009 mulching did not affect N uptake and decreased P uptake. Soil microbial biomass and activities of urease, beta-glucosidase and phosphatase at the 0-15 cm depth were generally higher during vegetative growth but lower during reproductive growth under mulch treatments than no mulch. Mulching treatments increased carbon (C) loss of buried maize residues (marginally by 5-9%), and decreased light soil organic C (15-27%) and carbohydrate C (12-23%) concentrations and mineralizable C and N (8-36%) at harvest in the 0-20 cm depth compared with no mulch, indicating that mulching promotes mineralization and nutrient release in soil during cropping seasons. As a result of these biological changes, mineral N concentration under mulch was markedly increased after sowing in upper soil layers compared with no mulch. Therefore, our results suggest that mulched cropping stimulated soil microbial activity and N availability, and thus contributed to increasing maize grain yield and nutrient uptake compared with no mulch.