A classification system is often used to reduce the number of different ecosystem types that governmental agencies are charged with monitoring and managing. We compare the ability of several different hydrogeomorphic (HGM)-based classifications to group lakes for water chemistry/clarity. We ask: (1) Which approach to lake classification is most successful at classifying lakes for similar water chemistry/clarity? (2) Which HGM features are most strongly related to the lake classes? and, (3) Can a single classification successfully classify lakes for all of the water chemistry/clarity variables examined? We use univariate and multivariate classification and regression tree (CART and MvCART) analysis of HGM features to classify alkalinity, water color, Secchi, total nitrogen, total phosphorus, and chlorophyll a from 151 minimally disturbed lakes in Michigan USA. We developed two MvCART models overall and two CART models for each water chemistry/clarity variable, in each case comparing: local HGM characteristics alone and local HGM characteristics combined with regionalizations and landscape position. The combined CART models had the highest strength of evidence (ω(i) range 0.92-1.00) and maximized within class homogeneity (ICC range 36-66%) for all water chemistry/clarity variables except water color and chlorophyll a. Because the most successful single classification was on average 20% less successful in classifying other water chemistry/clarity variables, we found that no single classification captures variability for all lake responses tested. Therefore, we suggest that the most successful classification (1) is specific to individual response variables, and (2) incorporates information from multiple spatial scales (regionalization and local HGM variables).