Water quality assessments are essential for providing information regarding integrated water resource management processes. This study presents the results of a spatial and seasonal surface water quality assessment of the Burío river sub-catchment in Costa Rica. Fourteen sample campaigns were conducted at eight sample sites between 2005 and 2010. Seasonal variations were evaluated using linear mixed-effects models where dissolved oxygen, total solids, and nitrate showed significant differences between dry and wet seasons (p < 0.05). Cluster analysis identified three clusters at the top, middle, and bottom of the catchment that were consistent with land use patterns, and principal component analysis identified the main parameters that were affecting 84% of the total variance in water quality (biochemical oxygen demand, dissolved oxygen, total phosphate, and nitrate). The National Sanitation Foundation Water Quality Index (NSF-WQI) results indicated the majority of the river consisted of mainly “medium” water quality, although “bad” and “good” water quality results were identified depending on sample site and season. This methodological approach provides a useful monitoring technique for local governments that can be used for further remediation strategies.