Coastal estuaries accumulate contaminants mobilised by intensive land use, yet the degree to which landscape context predicts contaminant burden in oysters at regional scales remains poorly quantified. We examined tissue toxicity and trace element concentrations in oysters (Saccostrea spp.) across six southern Queensland estuaries spanning a gradient of landscape modification. Toxicity was quantified using the BLT-Screen bioassay and 17 trace elements were measured by ICP-MS. Toxicity varied approximately four-fold among estuaries, with proximity to urban centres the strongest positive landscape correlate and total catchment conservation cover the strongest negative correlate. Full-subsets generalised additive models identified cobalt and copper as primary elemental predictors of toxicity, while a distinct anthropogenic metal cluster (Fe, Ba, V, Pb) was associated with reduced body condition. Arsenic diverged from anthropogenic metals, aligning with natural catchment characteristics consistent with marine arsenobetaine cycling. Buffer-scale land use (1–10 km) strongly predicted individual element concentrations, whereas overall toxicity integrated cumulative inputs across the full drainage area. These results demonstrate that regional landscape context strongly covaries with estuarine contamination and oyster condition, with direct implications for spatial prioritisation of reef restoration and catchment biomonitoring.