Anthropogenic activities and land-use change have exhibited significant impacts on estuarine ecosystems. Like many tropical estuarine systems, the Perancak estuary in Bali, Indonesia, experiences substantial seasonal water quality variations. In the current study, seasonal variation in water quality across three zones: the upper (U.E.), middle (M.E.), and lower (L.E.) of the estuary, representing residential areas, mangrove, and aquaculture ecosystems from January to December 2018, were observed. Principal component analysis was used to determaine the variable relationship at each station. The results showed that water quality generally declined during the dry and transition (dry to wet) seasons. This decline occurred mainly during hypoxia in the U.E. zone, indicating a combination of natural and anthropogenic factors. The main natural factor that influences water quality is rainfall. Anthropogenic and vegetation cover factors play equally important roles in the health of estuary ecosystems. The importance of tropical estuary health will become increasingly evident, requiring a thorough understanding of healthy ecosystem functions and management. Effective management and regulation of activities around estuary ecosystems are crucial to protect water quality and the health of these ecosystems.