Mechanistic hydrologic and water quality models provide useful alternatives for estimating water quality in unmonitored streams. However, developing these elaborate models for large watersheds can be time-consuming and expensive, in addition to challenges that arise during calibration when there is limited spatial and/or temporal monitored in-stream water quality data. The main objective of this research was to investigate different approaches for developing multivariate analysis models as alternative methods for rapidly assessing relationships between spatio-temporal physical attributes of the watershed and water quality conditions in monitored streams, and then using the developed relationships for estimating water quality conditions in unmonitored streams. The study compares the use of various statistical estimates (mean, geometric mean, trimmed mean, and median) of monitored water quality variables to represent annual and seasonal water quality conditions. The relationship between these estimates and the spatial data is then modeled via linear and non-linear multivariate methods. Overall, the non-linear techniques for classification outperformed the linear techniques with an average cross-validation accuracy of 79.7%. Additionally, the geometric mean based models outperformed models based on other statistical indicators with an average cross-validation accuracy of 80.2%. Dividing the data into annual and quarterly datasets also offered important insights into the behavior of certain water quality variables impacted by seasonal variations. The research provides useful guidance on the use and interpretation of the various statistical estimates and statistical models for multivariate water quality analyses.