The Florida Everglades is an environmentally sensitive wetland ecosystem with a number of threatened and endangered fauna species susceptible to the deterioration of water quality. Several potential toxic metal sources exist in the Everglades, including farming, atmospheric deposition, and human activities in urban areas, causing concerns of potential metal exposure risks. However, little is known about the pollution status of toxic metals/metalloids of potential concern, except for Hg. In this study, eight toxic metals/metalloids (Cd, Cr, Pb, Ni, Cu, Zn, As, and Hg) in Everglades soils were investigated in both dry and wet seasons. Pb, Cr, As, Cu, Cd, and Ni were identified to be above Florida SQGs (sediment quality guidelines) at a number of sampling sites, particularly Pb, which had a level of potential risk to organisms similar to that of Hg. In addition, a method was developed for quantitative source identification and controlling factor elucidation of toxic metals/metalloids by introducing an index, enrichment factor (EF), in the conventional multiple regression analysis. EFs represent the effects of anthropogenic sources on metals/metalloids in soils. Multiple regression analysis showed that Cr and Ni were mainly controlled by anthropogenic loading, whereas soil characteristics, in particular natural organic matter (NOM), played a more important role for Hg, As, Cd, and Zn. NOM may control the distribution of these toxic metals/metalloids by affecting their mobility in soils. For Cu and Pb, the effects of EFs and environmental factors are comparable, suggesting combined effects of loading and soil characteristics. This study is the first comprehensive research with a vast amount of sampling sites on the distribution and potential risks of toxic metals/metalloids in the Everglades. The finding suggests that in addition to Hg other metals/metalloids could also potentially be an environmental problem in this wetland ecosystem.