Cotton is the major fiber and oil seed crop around the globe, which is badly affected by water deficit stress. To fulfill the needs of increasing population with depleting water resources there is need to adopt management strategies which result in sufficient cotton yield with less water consumption. Keeping in view the current circumstances, research studies were conducted to evaluate the effects of partial rhizosphere drying (PRD) in combination with different mulch materials (M0= control, M1= black plastic mulch, M2= wheat straw mulch and M3= cotton stick mulch) for enhancing the productivity of cotton with less water. Study was comprised of five experiments. In the first experiment five different cotton cultivars (FH142, IUB222, IUB13, MM58, NOOR) from recent existing pool were screened out against control (I0) and PRD (I1) irrigation under wire house conditions. Cotton variety MM58 performed the best with maximum physiological and both enzymatic and nonenzymatic antioxidants values. In second experiment the selected variety (MM58) was again tested under various mulches and irrigation regimes in wire house. Wheat straw mulch gave the best results with maximum stomatal conductance, photosynthesis, and biochemical activities. Third experiment was carried out for comparative study of full, deficit and PRD irrigation. PRD was found better than DI (deficit irrigation) using equal amount of water. Abscisic acid (ABA) concentration was found more in PRD than DI which had positive influences on cotton physiology for efficiently utilization of irrigation water. Same experiment was repeated under field conditions for consecutive two years. More growth traits were found under control irrigation but yield attributes were statistically at par in both control and PRD irrigation. Concentration of osmolytes (proline & sugar contents), activities of antioxidant enzymes and water use efficiency (WUE) were more in PRD treatment. Amongst all mulches wheat straw mulch significantly improved the growth, yield and quality attributes (fiber length and strength) of cotton as compared to un-mulched treatment under field conditions. Economic analysis of the field experiments revealed that maximum net field benefit (NFB) was obtained in control irrigation with wheat straw mulch. It was concluded that wheat straw mulch gave the best results under both control and PRD irrigation than other mulch combinations used in the experiment.