The present study aims at the assessment of environmental quality of the most polluted stretch of river Yamuna along the megacity of Delhi. The study was conducted in order to examine toxicity and health hazards associated with persistent pollutants present in the fluvial ecosystem. Eighty four sediment and 56 vegetable samples from same locations were collected from the Delhi segment of river Yamuna flood plain in order to examine 20 organochlorine pesticides (OCPs) and 9 heavy metals (Cd, Co, Cr, Cu, Fe, Mn, Ni, Pb and Zn). Both the organic and inorganic groups of persistent toxic substances were monitored and analysed for the extent of eco-toxicological as well as dietary health risks posed to the local population. Eco-toxicological assessment was done based on sediment quality guidelines, enrichment factor, geo-accumulation index, degree of contamination and Pollution Load Index. The dietary-risk was assessed with the help of translocation factors (TF) of these pollutants in vegetables. Carcinogenic and non-carcinogenic health risks from consumption of vegetables were also investigated.The level of concern for heavy metals was greater than that of OCPs as per the sediment quality guidelines. DDT, Cd, Pb and Zn had maximum concentrations corresponding to level 3 of concern, while Cr and Ni reached up to the highest i.e., 4th level of concern. Sediment samples were found to be enriched and contaminated significantly with Cd and moderately with Pb, as represented respectively by enrichment factors and contamination factors (CF). CF for metals lied in order Zn > Cd > CrNi > PbCu. Pollution load index was highest at the location lying on the exit point of Yamuna in Delhi. TF values greater than 1 were observed in majority of samples analysed for Ni, Cr, Cu and Zn. Spinach topped among vegetables in terms of metal contamination. Cd, Ni and Pb accumulated more in the roots, as against Mn, Zn, Cu and Cr which had higher accumulation in the shoots. Translocation factors were substantially high in vegetables for most of the OCPs, clearly indicating bioaccumulation and potential health risk to the consumers. Health risk to humans was assessed for non-carcinogenic and carcinogenic potentials from ingestion of vegetables. Hazard Quotient (HQ) > 1 due to radish (roots and leaves) and cauliflower consumption in children indicated non-carcinogenic risk. Hazard Index (HI) beyond 1 for all the vegetables (except onion leaves) confirmed substantial cumulative risk. Lifetime cancer risk (LCR) revealed moderate (spinach, radish, beet root and cauliflower) to low (all the others) levels of carcinogenic risk to humans. Cancer risks from γ-HCH, β- HCH, Hept, Hept Ep, Ald, p,p’-DDT, and Cr exposure through the food chain could be well established.