Chemical warfare agents (CWAs) remain a significant threat to military personnel, civilian populations, and public health systems due to their high toxicity and potential for mass casualties. This review compares the toxicological characteristics of sarin, a representative organophosphorus nerve agent, and Lewisite, an organoarsenic vesicant agent. Sarin exerts its toxicity primarily through irreversible inhibition of acetylcholinesterase, resulting in excessive accumulation of acetylcholine at cholinergic synapses and the development of acute cholinergic crisis characterized by miosis, bronchoconstriction, muscle fasciculations, seizures, respiratory failure, and death. In contrast, Lewisite induces cellular injury through the interaction of arsenic moieties with sulfhydryl-containing enzymes and proteins, disrupting essential metabolic pathways and leading to oxidative stress, tissue necrosis, vesication, respiratory injury, and systemic organ damage. The review discusses the physicochemical properties, toxicokinetics, biochemical mechanisms, clinical manifestations, diagnostic approaches, and medical management strategies associated with both agents. Historical incidents involving sarin and Lewisite are also examined to illustrate their operational significance and the challenges they pose to emergency preparedness and disaster response. Despite differences in their molecular targets and pathophysiological effects, both agents present substantial risks due to their rapid onset of toxicity and potential to overwhelm healthcare systems during large-scale exposures. A comprehensive understanding of these mechanisms is essential for improving risk assessment, clinical management, medical countermeasure development, and preparedness against chemical threats.