The efficacy of a water quality management strategy highly depends on the analysis of water quality data, which must be intensively analyzed from both spatial and temporal perspectives. This study aims to analyze spatial and temporal trends in water quality in Code River in Indonesia and correlate these with land use and land cover changes over a particular period. Water quality data consisting of 15 parameters and Landsat image data taken from 2011 to 2017 were collected and analyzed. We found that the concentrations of total dissolved solid, nitrite, nitrate, and zinc had increasing trends from upstream to downstream over time, whereas concentrations of parameter biological oxygen demand, cuprum, and fecal coliform consistently undermined water quality standards. This study also found that the proportion of natural vegetation land cover had a positive correlation with the quality of Code River's water, whereas agricultural land and built-up areas were the most sensitive to water pollution in the river. Moreover, the principal component analysis of water quality data suggested that organic matter, metals, and domestic wastewater were the most important factors for explaining the total variability of water quality in Code River. This study demonstrates the application of a GIS-based multivariate analysis to the interpretation of water quality monitoring data, which could aid watershed stakeholders in developing data-driven intervention strategies for improving the water quality in rivers and streams.