As the proportion of renewable energy installations in modern power systems increases, major weather events can easily trigger significant fluctuations in new energy generation and electricity load, presenting the system with the dual challenges of ensuring power supply and renewable energy consumption. Traditional dispatch models need more coordination and optimization of flexible resources under major weather events and risk management of system operations. This study focuses on provincial-level transmission systems, aiming to achieve the coordinated and optimized dispatch of flexible resources across multiple time scales in response to the complex and variable environments faced by the system. Firstly, by profoundly analyzing the response mechanisms of power systems during major weather events, this study innovatively proposes an event-driven day-ahead and intra-day optimal dispatch strategy for power systems. This strategy can sense and respond to major weather events in the day-ahead phase and adjust dispatch decisions in real time during the intra-day phase, thereby comprehensively enhancing the adaptability of power systems to sudden weather changes. Secondly, by considering the variability of renewable energy sources and electricity demand in the day-ahead and intra-day dispatch plans, the strategy ensures efficient and reliable power system operation under normal and major weather event scenarios. Finally, the method’s effectiveness is validated using actual data from a provincial-level power grid in China. The proposed dispatch strategy enhances the resilience and adaptability of power systems to major weather events, which are becoming increasingly frequent and severe due to climate change. The research demonstrates that an event-driven day-ahead and intra-day optimal dispatch strategy can enhance the economic efficiency and robustness of power system operations through the coordinated dispatch of flexible resources during major weather events, thereby supporting the transition toward sustainable energy systems that are resilient against the challenges of a changing climate.