Toxic trace element exposure occurs through release of the ubiquitous and naturally occurring elements arsenic (As), cadmium (Cd), lead (Pb), and mercury (Hg). The unique environmental conditions of the wetland ecosystems along the southeastern Atlantic coast of the United States lead to the accumulation of Hg which is greater than in most other ecosystems in the country. There are also point sources of As, Cd, and Pb in this region. To effectively monitor trace element concentrations, and consequently the potential human exposure, accessible local sentinel species are needed. In this study, concentrations of As, Cd, Pb, Hg and six other trace elements (Al, Ni, Cu, Zn, Se, Mo) were examined in American alligators (Alligator mississippiensis) from seven wetland sites in South Carolina and Florida and assessed for their utility as a sentinel species for human trace element exposure. Alligators were chosen as a potential sentinel as they share a common exposure with the local human population through their aquatic diet, and they are directly consumed commercially and through recreation hunting in this region. Sex was significantly related to the concentration of Zn, Mo, and Al, but not As, Pb, Hg, Cd, Se, or Cu. Site specific differences in element concentrations were observed for As, Pb, Hg, Cd, Se, Zn, and Mo. Size/age was significantly related to the element Hg and Pb concentrations observed. The observed concentration ranges for the four toxic elements, As (6–156 ng/g), Cd (0.3–1.3 ng/g), Pb (3–4872 ng/g), and Hg (39–2765 ng/g), were comparable to those previously reported in diverse human populations. In this region alligators are hunted recreationally and consumed by the local community, making them a vehicle of direct human toxic element exposure. We propose that the similarity in As, Cd, Pb, and Hg concentrations between alligators observed in this study and humans underscores how alligators can serve as a useful sentinel species for toxic element exposure.