The aim of this work was to study the physiological, yield and quality responses of two upland cotton cultivars (Greek and Australian), grown on light-textured soil under irrigated, Mediterranean conditions, to three potassium levels (0, 80, 160 kg K2O ha−1). Despite its pivotal role in plant physiology and growth, K supplementation is often neglected by growers due to high cost and complexity with identifying optimal K levels. A rate of 80 kg K2O ha−1 was adequate to increase both seedcotton and lint yield and improve fiber length. This was despite the absence of any response of leaf cation concentrations (K, Na, Ca, Mg, their sum and ratios) to K fertilization. On a contrary, K application affected leaf gas exchange physiology by increasing CO2 assimilation rate and stomatal conductance thus leading to reduced leaf temperature and higher leaf water potential and carbon isotope discrimination (Δ). Cultivars did not differ in the leaf gas exchange characteristics and yield but the Australian (Carmen) had markedly better fiber quality, was water conservative and sustained higher leaf K concentrations compared to Greek (Elina). Growth stage (first open flower, full bloom, first open bolls) impacted significantly leaf gas exchange physiology and cation concentrations resulting in reductions of CO2 assimilation rate, stomatal conductance, leaf water potential, specific leaf area (SLA) and N and K concentrations through the growing season. Regardless the growth stage, the lint yield was negatively correlated with Δ, Na and Na/Mg ratio highlighting the importance of the conservative use of water on cotton yield and the detrimental role of Na despite the theoretical cotton's tolerance. Fiber length was closely correlated to leaf K at the first open boll stage indicating a putative deficiency of K which possibly accelerates cotton maturity. Overall, results of the present work emphasize the essentiality of adequate K supply for cotton physiology, growth, yield and quality, highlight the interactions of K with other nutrients and stress the cultivar selection as a means to encounter soil K inadequacy.