The Mekong Delta region is increasingly challenged by a declining and irregular water budget over recent decades. This trend is evidenced by altered precipitation patterns, characterized by drier wet seasons and wetter dry seasons, along with diminished upstream flow and a shifting wet season flood pulse. This study presents a comprehensive analysis of water level trends at the Tan Chau station on the Mekong River and the Chau Doc station on the Bassac River in Vietnam's Upper Mekong Delta Region from 2000 to 2023. Our findings reveal a significant decline in annual water level metrics (Hmax, Hmin, and Have) at both stations, with the exception of the lowest water level (Hmin) at Chau Doc. Particularly, the wet season (August-November) shows the most pronounced decreases across all monthly water level indicators, with a steeper decline observed at Tan Chau than Chau Doc. These trends, with annual decreases ranging from −7.14 to −9.32 cm/year, underscore the urgent need for adaptive water resource management and robust disaster risk mitigation strategies in the Mekong Delta Region.