• DSSAT CROPGRO-Cotton model was evaluated using in-season crop growth and crop yield data. • Average percent error of <15% was achieved for all target categories during evaluation. • Four irrigation strategies were evaluated using the evaluated model. • TTT-7.5 h 12 mm simulated irrigation strategy had the highest water use efficiency. • ET-95% simulated irrigation strategy had the lowest water use efficiency. The Texas High Plains (THP) region, a vital part of U.S. grain and fiber production, is experiencing the effects of conflicting interests in the diminishing Ogallala Aquifer, making necessary the adoption of more efficient irrigation strategies. Decision Support System for Agrotechnology Transfer (DSSAT) is a process-based model that uses meteorological, soil, and crop management data to predict crop growth, development, and yield. A well-evaluated DSSAT model is useful for simulation of efficient crop and irrigation management strategies. This study details the evaluation of CROPGRO-Cotton module in the DSSAT model based on measured in-season biomass and canopy height, and crop yield data from a field study as well as the use of the evaluated model for determining the best irrigation strategy for cotton (Gossypium hirsutum L. var. hirsutum) in terms of crop yield and irrigation water use efficiency. Irrigation simulation experiments were conducted over a testing range for four separate irrigation scheduling strategies —Time Temperature Threshold (TTT)-5.5 h, TTT-7.5 h, Daily Irrigation (DI), and percent ET replacement —to determine the most efficient irrigation strategy that results in maximum yield with minimum irrigation water input. The DSSAT CROPGRO-Cotton model demonstrated potential to simulate the effects of various irrigation strategies on cotton yield and water use efficiency. The 12 mm, 7.5 h TTT strategy was found to be the best strategy to achieve a maximized yield with the greatest irrigation water use efficiency, with a modelled yield of 5887 kg ha−1 using 195 mm of irrigation throughout the season. [ABSTRACT FROM AUTHOR]