Resistance to environmental stress is one of the most important forces molding the distribution and abundance of species. We investigated the evolution of desiccation stress resistance using 20 outbred Drosophila melanogaster populations directly selected in the laboratory for adult desiccation resistance (D), postponed senescence (O), and their respective controls (C and B). Both aging and desiccation selection increased desiccation resistance relative to their controls, creating a spectrum of desiccation resistance levels across selection treatments. We employed an integrative approach, merging data on the life histories of these populations with a detailed physiology of water balance. The physiological basis of desiccation resistance may be mechanisms enhancing either resource conservation or resource acquisition and allocation. Desiccation-resistant populations had increased water and carbohydrate stores, and showed age-specific patterns of desiccation resistance consistent with the resource accumulation mechanism. A significant proportion of the resources relevant to resistance of the stress were accumulated in the larval stage. Males and females of desiccation-selected lines exhibited distinctly different patterns of desiccation resistance and resource acquisition, in a manner suggesting intersexual antagonism in the evolution of stress resistance. Preadult viability of stress-selected populations was lower than that of controls, and development was slowed. Our results suggest that there is a cost to preadult resource acquisition, pointing out a complex trade-off architecture involving characters distributed across distinct life-cycle stages.