Rice, as a globally vital food crop, is frequently threatened by flooding, which adversely affects its growth and yield. The most immediate and prominent influence of waterlogging or submergence induced by flooding on rice is hypoxia (reduced oxygen availability) or anoxia (absence of oxygen) stress and the consequent energy deficiency. Rice has evolved specific acclimation strategies to counteract or alleviate flooding stress, including leaf gas film (LGF) formation, adventitious root (AR) emergence, aerenchyma formation, radial oxygen loss (ROL) barrier development, and the stunted or elongated growth of coleoptiles or internodes, all of which serve to secure oxygen supply and maintain energy homeostasis for sustaining survival. These adaptive traits and strategies are governed by the regulatory genes involved in the reprogramming of energy and carbohydrate metabolism, the accumulation and scavenging of reactive oxygen species (ROS), and the programmed cell death (PCD) process, as well as the phytohormone biosynthesis and signaling pathways. To facilitate a comprehensive understanding of the submergence response and tolerance and the intricate regulatory mechanisms in rice, this review integrates the impacts of flooding on the growth and development, the strategies employed to adapt to submergence, the physiological and biochemical characteristics, the phytohormonal signaling and crosstalk, and the molecular mechanistic framework of rice subjected to submergence stress. It also highlights the importance of key superior genes for flooding-tolerance, flooding-tolerant germplasms, and molecular breeding technologies in developing submergence-tolerant rice varieties. By aligning these advances, this review provides valuable insights into and guidance for improving resilience to submergence stress and enhancing crop production under constantly changing climate conditions.