The uncertainty brought about by the high proportion of distributed generations poses great challenges to the operational safety of novel distribution systems. Therefore, this paper proposes an online reactive power and voltage control method that integrates source–load uncertainty and a mechanism–data hybrid drive (MDHD) model. Based on the concept of a mechanism and data hybrid drive, the mechanism-driven deterministic reactive power optimization strategy and the stochastic reactive power optimization strategy are used as training data. By training the data-driven CNN–GRU network model offline, the influence of source–load uncertainty on reactive power optimization can be effectively assessed. On this basis, according to the online source and load predicted data, the proposed hybrid-driven model can be applied to quickly obtain the reactive power optimization strategy to enable fast control of voltage. As observed in the case studies, compared with the traditional deterministic and stochastic reactive power optimization models, the hybrid-driven model not only satisfies the real-time requirement of online voltage control, but also has stronger adaptability to source–load uncertainty.