The linkage between the land use/land cover (LULC) pattern and water quality is an emerging topic in multidisciplinary research. The LULC changes affect water quality in many ways. Change in the land use/land cover, especially urbanization leads to water quality deterioration. This study mainly focuses on the water quality in parts of the river Karamana, which flows through the Thiruvananthapuram urban area. The water quality parameters of six selected sites within the urban area were obtained. Physico-chemical and biological parameters of water quality were analysed for 2019 (pre-monsoon, monsoon, and post-monsoon). The water quality data obtained during the present study were used to characterize the built-up and other areas. Results have shown a distinct variation of parameters in the upstream region (less built-up) than that of the urban area (more built-up). The results have clearly demonstrated the indication of the effect of urbanization on water resources. The speedy development of urban built-up in Thiruvananthapuram city causing severe issues to the water regime in terms of its quality. The data shows that the water quality is poor in the pre-monsoon period in most of the areas. Though the worsening of water quality is limited to a few localized zones, the trend of the quality change is serious. It needs the attention and proper consideration of policy planners and decision-makers. Adequate effluent treatment facilities in the urban regions is the need of the hour to minimize pollution.