As part of the International Decade for Action “Water for Sustainable Development” (2018–2028), assessing the water and irrigation potential of river basin catchment areas is essential for sustainable water use and agricultural development. This study assesses the water and irrigation potential of the Karatal River Basin in the Zhetysu Region of the Republic of Kazakhstan using trend analysis of climatic and hydrological indicators considered as functions of time, providing a basis for forecasting. Source data for this study were obtained from yearbooks published by the “Kazhydromet” and from the regional water management organization “Kazvodkhoz”. Analysis of the spatial and temporal variability of climatic and hydrological indicators revealed both stochastic and deterministic components, with the latter expressed as significant trends, providing a basis for assessing the water and irrigation potential of river basin catchments. For the entire period from 1966 to 2024, the estimated total increase in the average annual air temperature at the meteorological stations under study, determined based on a linear trend, ranged from 1.444 to 6.078 °C. Annual precipitation showed mixed trends, with linear trend coefficients ranging from −2.916 to +1.989 mm/year. The estimated total decrease in the average annual flow of the Karatal River, determined based on a linear trend over the same period, was 15.658 m³/s at the Ushtobe hydrological station and 31.575 m³/s at the Naimansuek station. The river discharge decrease occurred against a backdrop of rising average annual air temperatures and changes in precipitation patterns, which affected the components of the basin’s water balance, including river discharge and evaporation. Based on the identified trends and indicators of the spatial organization of water use, the water availability of the Karatal River Basin was assessed using the water stress index and the per capita water availability indicator—the Falkenmark index. The volume of available water resources per capita ranged from 32.233 to 5.872 thousand m³ per person per year in the Eskeldi District and from 87.826 to 44.814 thousand m³ per person per year in the Karatal District. The water stress index ranged from 21.130% to 13.096% and from 19.10% to 2.848%, respectively, indicating water stress levels ranging from moderately high to moderately low and from moderately low to low. An assessment of trends in the dynamics of climatic and hydrological indicators, as well as criteria for water resource availability, revealed differences in the structure of water use among administrative districts.