Atmospheric emissions from freight transportation contribute to human health and climate damage. Here, we quantify and compare three environmental impacts from inter-regional freight transportation in the contiguous United States: mortality attributable to PM2.5 air pollution, racial-ethnic disparities in mortality from PM2.5, and CO2 emissions. We compare all major transportation modes (truck, rail, barge, aircraft) and all major inter-regional routes (~30,000 routes). Our study is the first to comprehensively compare each route separately, and the first to explore racial-ethnic exposure disparities by route and mode, nationally. Impacts (health, health-disparity, climate) per tonne of freight are largest for aircraft. Among non-aircraft modes, per tonne, rail has the largest health and health-disparity impacts and the lowest climate impacts, whereas truck transport has the lowest health impacts and greatest climate impacts – an important reminder that health and climate impacts are often but not always aligned. For aircraft and truck, average monetized damages per tonne are larger for climate impacts than for PM2.5 air pollution; for rail and barge, the reverse holds. We find that average exposures for inter-regional truck and rail are the highest for White non-Hispanic people, from barge is highest for Black people, and from aircraft is highest for people who are mixed/other race. Level of exposure and disparity among racial-ethnic groups vary in urban and rural areas. This research can be used to inform, for a given inter-regional origin and destination, which freight mode offers the lowest environmental health, health-disparity, and climate impacts.