In this work, hybrid nanocomposites of CuS QDs @ ZnO photocatalysts are fabricated through a facile microwave-assisted (MW) hydrothermal method as a green preparation process. The prepared photocatalysts (PCs) are employed under simulated sunlight (SL) for the degradation of ciprofloxacin, ceftriaxone, ibuprofen pharmaceuticals, methylene blue dye, and 2,4,5-trichlorophenoxyacetic acid (2,4-D) pesticide. The prepared photocatalysts are characterized in detail using several compositional, optical, and morphological techniques. The influence of the CuS (QDs) wt. % on morphological, structural, as well as photocatalytic degradation efficiency have been investigated. The small displacement between the (107) plane of CuS and the (102) plane of ZnO can confirmed the existence of lattice interaction, implying the formation of p-n heterojunctions. TEM and XRD results demonstrated that the CuS QDs are established and uniformly decorated on the surface of ZnO NRs, confirming the forming of an efficient CuS QDs @ ZnO heterojunction nanostructures. The CuS QDs @ ZnO hybrid nanocomposites showed enhancement in crystallinity, light absorption, surface area, separation of e–h pair and inhibition in their recombination at an interfacial heterojunction. In addition it is found that, 3 wt% CuS QDs @ ZnO has the foremost influence. The results showed improvement of photocatalytic activity of the 3% CuS QDs @ ZnO hybrid nanocomposite as compared to the bare ZnO nanorods. The impressive photocatalytic performance of CuS @ ZnO heterostructure nanorods may be attributed to efficient charge transfer. The prepared CuS QDs @ ZnO hybrid nanocomposites exhibited 100% removal for MB dye, after 45 min, and after 60 min for ibuprofen, ciprofloxacin pharmaceuticals, and 2.4.5 trichloro phenoxy acetic acid pesticide with the catalyst amount of 0.2 g/L. Although 100% removal of ceftriaxone pharmaceutical acheived after 90 min. In addition CuS QDs @ ZnO hybrid nanocomposites exhibited complete removal of COD for ibuprofen, ceftriaxone pharmaceuticals and 2.4.5 trichloro phenoxy acetic acid pesticide after 2 h with no selectivity. Briefly, 3% CuS QDs@ZnO hybrid nanocomposites can be considered as promising photoactive materials under simulated sunlight for wastewater decontamination.