Amyotrophic Lateral Sclerosis (ALS) is an incurable, quickly progressing neurodegenerative disease characterized by the death of motor neurons. ALS affects approximately 1 in 400 people worldwide, and most ALS cases are sporadic (sALS) with no known causative factors. Previous work has indicated that the organochlorine pesticide cis-chlordane is found more often in the blood of sALS patients than controls (Su et al., 2016), however little is known about how environmental risk factors induce motor neuron death. Here we show that cis-chlordane is especially toxic to motor neurons in vitro and induces motor neuron degeneration and NMJ deficits in vivo using zebrafish. We find that stem-cell derived motor neurons are more sensitive to cis-chlordane than other cell types and show that cis-chlordane treatment toxicity is independent of its known antagonism at the GABAA receptor. Our transcriptomic analysis of motor neurons indicates that cis-chlordane treatment disrupts similar mechanisms to those previously observed in ALS, inducing ER and mitochondrial stress and perturbing ion homeostasis. Investigation of these perturbations in vitro indicates that autophagic activity and ROS levels increase with cis-chlordane treatment. Our results lay the groundwork for studying how environmental pollutants contribute to sporadic ALS etiology.