Climate-smart agriculture (CSA) improves agricultural productivity and enhance farm income on a sustainable basis, enhance water and nutrients use efficiency, resilient to climatic stresses, and lowering the emissions of Greenhouse Gas (GHG) to a minimum level. Water-smart, energy-smart, carbon-smart and knowledge-smart practices and technologies significantly contributed directly or indirectly to improve productivity, enhance resilience and reduce GHG emission. Cotton is one of the important cash crops of Pakistan. It is a climate sensitive crop and suffered by multiple shocks as climate change and market discrepancies during the last two decades. The present paper aimed to estimate and compare the resource use efficiency including technical, economic and water use efficiency of adopters of CSA and non-adopters in cotton production. The study was conducted along Lower Bari Doab Canal (LBDC) irrigation system in Punjab, Pakistan. First-hand information was gathered through a well-structured and comprehensive questionnaire from 133 adopters of CSA and 65 farmers cultivating cotton with traditional methods. Input-oriented Data Envelopment Analysis technique was employed to investigate the technical, economic and water use efficiency, assuming variable return to scale. The Bootstrap Truncated Regression was used to identify the factors influencing the resource use efficiency. The results showed that the adopters of CSA were using inputs more efficiently. The analysis revealed that adopters have higher cotton yield from per m3 irrigation water than non-adopters. Adopters were found to be financially sound, having easy access to credit and fast adaptation behavior towards environmental changes, and therefore, economically better off as compared to non-adopters. Bootstrap Truncated Regression analysis revealed that easy access to credit, provision of extension services, awareness regarding CSA, availability of good quality groundwater and right of ownership of tubewell were significantly affecting resource use efficiency. The finding suggested certain policy implications for creating awareness and financial support for the cotton growers to expedite the adaptation of CSA practices and technologies in the cotton growing area. This can enhance resource use efficiency, net farm income and livelihood of rural masses.