River discharge has an important influence on the chemistry of Arctic shelf seas and surface waters. In this study, we examined the changes in nutrient, trace metal, dissolved organic matter, dissolved inorganic carbon, alkalinity, and radium isotope distributions across the Mackenzie River delta and estuary in June 2016, and estimated trace element and isotopes fluxes from the Mackenzie River to the Western Arctic Ocean. While inorganic nutrient, dissolved inorganic carbon, alkalinity, trace metal, and radium levels remained fairly constant through the delta, dissolved organic matter concentrations were 2–3.5 times higher at the mouth of the river, reflecting inputs from the delta. In the estuarine mixing zone, radium isotope ratios indicated that both desorption from suspended sediments and benthic inputs affected solute concentrations. Similarly, most of the measured trace metals (Ba, Co, Cu, Mn, Ni) exhibited non-conservative addition in the freshwater-saltwater transition zone, while Pb was removed and U was mixed conservatively. Inorganic nutrients were affected by both addition and removal processes in the estuary. Dissolved inorganic carbon and alkalinity exhibited net removal, likely due to a combination of biological uptake, gas exchange, CaCO3 precipitation, and surface ion exchange processes. Approximately 45% and 60% of dissolved organic carbon and nitrogen, respectively, were removed rapidly at low salinities, in contrast with previous studies suggesting conservative mixing through Arctic estuaries. This study highlights the need to take deltaic and estuarine processes into account when determining the flux of riverine solutes to the coastal ocean.