Freely dissolved OCPs and PCBs were measured by using polyethylene passive samplers at 15 sites during 2014 throughout the stretch of the Indus River to investigate the spatial pattern and risk assess. Levels (pg/L) of dissolved ∑OCPs and ∑PCBs ranged from 34 to 1600 and from 3 to 230. Among the detected OCPs, dissolved DDTs (p,p′-DDE, followed by p,p′-DDT) predominated with levels of 0.48 to 220 pg/L. The order of occurrence for other studied OCPs was as follows: HCB, endosulfans, chlordanes, and HCHs. Spatially, dissolved (pg/L) ∑OCPs varied (p < 0.05) as the following: surface water of the alluvial riverine zone (ARZ) showed the highest levels (114) followed by the frozen mountain zone (FMZ) (52.9), low-lying zone (LLZ) (28.73), and wet mountain zone (WMZ) (14.43), respectively. However, our zone-wise PCB data did not exhibit significant differences (p > 0.05). Principal component analysis/multilinear regression results showed pesticide usage in the crop/orchard fields and health sector, electric and electronic materials, and widespread industrial activities as the main source of OCPs and PCBs along the Indus River. Our results showed that OCPs and PCBs contaminated water intake, playing an important role towards the considerable cancer/non-cancer risk (HI and CR values) along the Indus River Flood-Plain.