Drought is an important type of climate extreme that negatively affects crop production. Therefore, in order to meet the dietary requirements of the rising human population with diminishing water resources, there is the need to adopt techniques that optimize crop yield under reduced water conditions. The use of mulches and Partial root-zone drying irrigation (PRI) is imperative to increase crop yield under such low water conditions. Therefore a greenhouse experiment was carried out to determine the effect of mulching and reduced irrigation on wheat production in a semi-arid region (Bahawalpur, Pakistan). The experiment included four mulching treatments (un-mulched, black plastic sheet mulch, wheat straw mulch and cotton sticks mulch) and two watering regimes (normal watering and PRI technique that involves alternate watering to only one side of root zone only) arranged in a completely randomized design. Wheat growth (leaf area index, plant height), water related parameters (leaf relative water contents, leaf turgor potential) and physiological (chlorophyll contents, stomatal oscillation and photosynthetic rate) and biochemical processes were significantly higher with mulching than un-mulched for both irrigation levels. However, among the mulching treatments, the use of black plastic mulch gave the best results. Between the two irrigation levels, higher wheat growth, physiological and water related parameters were found with normal watering. Whereas leaf osmotic potential, quality traits and antioxidant enzymatic activities were higher with PRI. In conclusion, the harmful impacts of water deficit on wheat can be mitigated significantly with the application of mulches, particularly the use of black plastic mulch, with PRI.