The present work investigated the spatial distribution and ecological risk assessment of total and mild acid-leachable trace elements in surface sediments (top 0-10 cm; grain size ≤ 63 μm) along the Hooghly (Ganges) River Estuary and Sundarban Mangrove Wetland, India. The trace elements, analyzed by ICPMS, showed wide range of variations with the following descending order (mean values expressed in milligrams per kilogram): Fe (25,050 ± 4918) > Al (16,992 ± 4172) > Mn (517 ± 102) > Zn (53 ± 18) > Cu (33 ± 11) > Cr (29 ± 7) > Ni (27 ± 6) > Pb (14 ± 3) > As (5 ± 1) > Se (0.37 ± 0.10) > Cd (0.17 ± 0.13) > Ag (0.16 ± 0.19) > Hg (0.05 ± 0.10). In the acid-leachable fraction, Cd (92%) is dominated followed by Pb (81%), Mn (77%), Cu (70%), and Se (58%) indicating their high mobility, imposing negative impact on the adjacent benthos. The sediment pollution indices (both enrichment factor and contamination factor) suggested severe pollution by Ag at the sampling site Sajnekhali, a wildlife sanctuary in Sundarban. The mean probable effect level quotient indicated that surface sediments in the vicinity of the studied region have 21% probability of toxicity to biota. The result of multivariate analyses affirms lithogenic sources (e.g., weathering parent rocks, dry deposition) for As, Pb, Cr, Cu, and Ni, whereas Cd and Hg originated from anthropogenic activities (such as urban and industrial activities). Both human-induced stresses and natural processes controlled trace element accumulation and distribution in the estuarine system, and remedial measures are required to mitigate the potential impacts of these hazardous trace elements.