Abstract Prevalence of infection, limited choice of drugs, and emerging resistance against contemporary drugs lead to a pressing need to develop new anthelmintic drugs and drug targets. However, limited understanding of the physiology of worms has delayed the process substantially. Here, for the first time, we are reporting the tissue morphology of Haemonchus contortus and targeting its nervous system with quercetin, a naturally occurring flavonoid. Quercetin showed anthelmintic activity against all of the developmental stages of the H. contortus. Further, histological analysis demonstrated damage of various body parts, including isthmus, brut, pseudocoele, and other organs due to quercetin treatment. Mechanistic studies revealed the generation of oxidative stress and alterations in activities of the stress response enzymes, such as catalase, superoxide dismutase, and glutathione peroxidase. Moreover, the time-dependent imaging of ROS-generation disclosed neuropils as the primary targets of quercetin in the adult worms, which eventually lead to the paralysis and death of the worms. Thus, altogether, this work demonstrates that the nervous system of the parasitic helminth, H. contortus, is a novel target of the drug quercetin.