Shenzhen River (SZR) is a boundary river of two super-large modern cities and has important wetland ecological functions in the estuary, while it suffered unprecedented pollution during the past decades due to the rapid urbanizing of the catchment area. Twelve parameters of heavy metals (HMs), nutrients (N, P, TOC), and physicochemical indexes (pH, EC) of the SZR sediment from 8 typical sites were analyzed to explore their distribution, risk, and sources. The distribution of sediment parameters was closely related to the urban functional structure, basin topography, and anthropogenic control. Heavy metals (HMs) of SZR sediment were in a contamination degree order of Cd> >Cu> Zn> Pb> Ni> Cr, a combined risk of HMs and tremendous organic threat concentrated at the upper and middle reaches in the lower layer. HMs and nutrients in SZR sediments showed strong inner correlations but were limited influenced by physicochemical properties. Factor, clustering, and multiple linear regression analysis were comprehensively applied for the quantitative source apportionment. Industry-related sources and domestic wastewater were the major contamination sources, while the non-point sources like urban surface runoff, natural sources, and solid waste carrying should be paid special attention to considering their maintained increasing risk.