Nanoscale zero-valent iron (nZVI) is one of the most extensively applied nanomaterials for groundwater and hazardous waste treatment. Despite its high potential for environmental applications, there is limited knowledge about the fundamental properties of nZVI, particularly, its structure, surface composition, and changes in these characteristics in the aqueous media as the nanoparticles interact with aqueous contaminants. This research aims to investigate the structure and surface chemistry of nZVI and to understand how these attributes influence the material's reactivity towards various water contaminants. This work first involved a detailed examination of the metallic-core-oxide-shell structure using a variety of microscopic and spectroscopic tools. It was found that the polycrystalline metallic iron nuclei are spontaneously enclosed by a disordered layer of iron oxide that is 2–3 nm thick. Using a group of water contaminants (Hg(II), Zn(II) and hydrogen sulfide) as molecular probes, it was shown that the nanoparticles were able to utilize multiple pathways including adsorption, precipitation, reduction and surface mineralization to effectively immobilize these contaminants. The observed multiplexed reactivity is imparted by the particular core-shell configuration allowing both the oxide and metal components to exert their reactive tendency without undue kinetic hindrance. The second theme of this research was to examine the structural changes experienced by Pd-doped nZVI during exposure to aqueous media. With scanning-TEM X-ray energy-dispersive spectroscopy (STEM-XEDS), the translocation of Pd from the surface to regions underneath the oxide layer and the rapid loss of the Fe(0) core due to accelerated aqueous corrosion were observed. The morphological changes resulted in a severe reduction in the reductive dechlorination rate of trichloroethylene (TCE), suggesting that the activity of Pd-doped nZVI is a dynamic function of time and particle structure. The close relationship between the structure and reactivity of nZVI is further illustrated by reactions with aqueous arsenite (As(III)). Notably, nZVI caused simultaneous oxidation and reduction of arsenite in the solid phase. Using depth-resolved high-resolution X-ray photoelectron spectroscopy (HR-XPS), multi-layered distributions of different arsenic valence states in the nanoparticles were observed, where the oxidized arsenic (As(V)) was predominantly present at the surface and the reduced form (As(0)) was located at the oxide/metal interface. The observed dual redox capability is therefore enabled by the metal core and oxide layer independently. The findings presented in this work establish that nZVI possesses more complex functionality than bulk-scale ZVI or iron oxides. The improved understanding of sequestration mechanisms studied here may inform optimal design of nZVI treatment systems and aid development of materials and new applications.