The Buyuk Menderes River (BMR) is one of the largest rivers in Turkey. This river irrigates efficient farmlands and includes tributaries of other rivers and streams and many populated towns within its limits in the Egc region. Both the estuary and Isikli Lake serve as a sanctuary for various waterbirds. Therefore, the BMR plays a critical role both for the inhabitants and for the ecosystem organisms in its environs. In the present study, we analyzed levels of metals including iron, barium, zinc, vanadium, cobalt, chromium, cadmium, copper, nickel, aluminum, arsenic, manganese, antimony, silver, selenium, boron, mercury, titanium, and lead in river water, sediment, fish (Cyprinus carpio; common carp), and in various waterbird (Fulica atra, Euroasian coot; Larus michahellis, yellow-legged gull; Ardea cinerea, grey heron; Larus melanocephalus, Mediterranean gull; and Pelecanus crispus, pelican) samples. Analyses were performed using an inductively coupled plasma-mass spectrometry (ICP-MS) instrument after sample preparation. Comparing metal concentrations among different sample types, it was found that barium, aluminum, and zinc are the major metals in river water, and zinc in common carp muscle, while iron, aluminum, and manganese are the major metals in sediments. Iron, zinc, copper, and aluminum were the highest in waterbird muscle tissue. Iron and barium were found to be the major metals in eggshell, while iron and zinc are the major metals in egg samples. A simple Bworst-case scenario" model of risk assessment revealed that some of the analyzed metals may pose a risk for human health through consuming fish.