Background In March 2020, the World Health Organization declared the coronavirus disease 2019 (COVID-19) to be a pandemic, stating that those with underlying health conditions are most susceptible, including motor neuron disease (MND). Objective To examine the effect the COVID-19 pandemic had on deaths from MND in the United States. Methods Death certificate data for all MND deaths aged 20 years and older were analyzed from 2017 to 2019 (pre-COVID), then expanded to include 2020 and 2021 (COVID) deaths to evaluate if COVID-19 impacted MND deaths. Results The average number of MND deaths documented during the COVID-19 years was 8009, up from 7485 MND deaths pre-COVID. The age-adjusted mortality rate among the non-Hispanic population increased during COVID to 2.78 per 100,000 persons (95% CI = 2.73–2.82) from 1.81 (95% CI = 1.78–1.84). The Hispanic population also saw an increase in mortality rate during COVID (1.61, 95% CI = 1.51–1.71) compared with pre-COVID (1.10, 95% CI = 1.03–1.17). Decedent’s home as a place of death also saw a mortality rate increase during COVID (1.51, 95% CI = 1.48–1.54) compared with pre-COVID (1.30, 95% CI = 1.27–1.32). For the Hispanic population, the rate peaked at 80–84 years pre-COVID, but for the COVID years, the rate peaked earlier, at 75–79 years. Conclusion The total number of MND deaths was greater during COVID than in the preceding years. The analysis suggests there might have been a consequence of circumstances surrounding the global pandemic and the associated restrictions.