The Orcia River basin lies north of the Mt. Amiata mining district and may receive potentially harmful/toxic elements such as mercury (Hg) and arsenic (As) therefrom. The Orcia River eventually flows to the Ombrone River, which in turn flows to the Tyrrhenian Sea. The analysis of stream sediments collected in the Orcia River and its main tributaries, as well as in the Ombrone River, indicates moderate concentrations of both Hg and As (median values, Hg 118 μg/kg and As 5.25 mg/kg), rarely exceeding Italian environmental quality standards. Exceptionally high values for both elements are observed only in close proximity to the former Pietrineri Hg mine (Hg 195 mg/kg and As 35 mg/kg). Travertine and unconsolidated deposits associated with thermal springs in the area generally exhibit low Hg concentrations (4–320 μg/kg), with a significant exception of 23 mg/kg at Bagni San Filippo. Arsenic concentration in the same deposits is more variable with a peak level of 358 mg/kg. Surface waters collected at the same sites as stream sediments show Hg and As concentrations below the Italian mandatory limits for drinking waters (1 μg/L for Hg and 10 μg/L for As). Likewise, in thermal springs, Hg concentrations are low, whereas As concentrations are relatively high (up to 23.4 μg/L), which is in agreement with previous studies. At present, the input of toxic elements from the mining district into the Orcia and Ombrone watersheds is lower than inputs documented in the Paglia and Tiber catchments south of Mt. Amiata and does not pose an immediate environmental threat. However, the possible remobilization of Hg-contaminated sediments during flash flood events cannot be dismissed.