Public transit buses, which move more than 5 billion passengers annually in the United States (U.S.), can contribute substantially to the environmental health burden through emitted air pollutants. As a leader in transforming to cleaner bus fleets, the Regional Transport Commission of Southern Nevada (RTC) has been transitioning from diesel to compressed natural gas (CNG) transit buses since 1999. By 2017, ~75% of RTC’s buses operating in Clark County, Nevada were CNG-powered. This study assesses the health benefits of the venture using the US Environmental Protection Agency’s (EPA) Co-Benefits Risk Assessment (COBRA) model, considering the emission and exposure changes from the 2017 baseline for two hypothetical scenarios: (1) no transition (CC_D) and (2) complete transition (CC_N). The CC_D scenario shows realized health benefits, mostly due to avoided mortality, of 0.79–8.21millionperyearfor2017alone,whileCCNsuggestsanadditional0.88–2.24 million annually that could be achieved by completing the transition. The wide range of estimates partly reflects uncertainties in determining diesel bus emissions under business-as-usual. These health benefits were not limited locally, with ~70% going to other counties. Two national-scale scenarios, US_D and US_N, were also constructed to explore the health impact of transitioning from diesel to CNG buses across the U.S. As of 2017, with CNG powering only ~20% of transit bus mileages nationwide, there could be massive unrealized health benefits of $0.98–2.48 billion per year including 114–258 avoided premature deaths and \u3e5000 avoided respiratory and cardiovascular illnesses. Taking into account the health benefits, economic costs, and the inter-state nature of air pollution, expanding federal assistances to accelerate a nationwide transition to cleaner bus fleets is highly recommended