Segmentations divide a diverse resource into groups, or segments, based on distinctive attributes that may respond similarly to management actions. A 4-way segmentation based on lake origin (natural or artificial) and size (small or large) was constructed for Mississippi lakes using a 30 yr data set. We aimed to document elements distinguishing these segments to understand relationships among them and to seek insight into lake management that may be apparent at the segment scale but not at the lake scale. Analyses pinpointed differences among the 4 segments relative to nutrient levels, fish assemblage composition, fishery characteristics, angler catch, and fishery management objectives. In general, most artificial lakes were eutrophic, varied widely relative to species composition depending on whether they impounded small or large rivers, their fish assemblages could be heavily influenced by stocking, provided principally centrarchid fisheries, and the management focus was on angler harvest. Most natural lakes were hypereutrophic, included higher species richness, provided a greater diversity of fisheries, and the management focus was on fish populations and habitat. Fishing success was similar across segments. The group-wise differences substantiate the segmentation and bring into focus a new level of concepts not typically relevant when considering lakes in isolation, such as issues about lake quantities, similarities, and geographical distributions. The segmentation represents the framework needed for considering lakes as parts of a larger and interactive management system.