Ambient air pollution from ozone and fine particulate matter is associated with premature mortality. As emissions from one continent influence air quality over others, changes in emissions can also influence human health on other continents. We estimate global air-pollution-related premature mortality from exposure to PM2.5 and ozone and the avoided deaths due to 20 % anthropogenic emission reductions from six source regions, North America (NAM), Europe (EUR), South Asia (SAS), East Asia (EAS), Russia–Belarus–Ukraine (RBU), and the Middle East (MDE), three global emission sectors, power and industry (PIN), ground transportation (TRN), and residential (RES), and one global domain (GLO), using an ensemble of global chemical transport model simulations coordinated by the second phase of the Task Force on Hemispheric Transport of Air Pollutants (TF HTAP2), and epidemiologically derived concentration response functions. We build on results from previous studies of TF HTAP by using improved atmospheric models driven by new estimates of 2010 anthropogenic emissions (excluding methane), with more source and receptor regions, new consideration of source sector impacts, and new epidemiological mortality functions. We estimate 290 000 (95 % confidence interval (CI): 30 000, 600 000) premature O3-related deaths and 2.8 million (0.5 million, 4.6 million) PM2.5-related premature deaths globally for the baseline year 2010. While 20 % emission reductions from one region generally lead to more avoided deaths within the source region than outside, reducing emissions from MDE and RBU can avoid more O3-related deaths outside of these regions than within, and reducing MDE emissions also avoids more PM2.5-related deaths outside of MDE than within. Our findings that most avoided O3-related deaths from emission reductions in NAM and EUR occur outside of those regions contrast with those of previous studies, while estimates of PM2.5-related deaths from NAM, EUR, SAS, and EAS emission reductions agree well. In addition, EUR, MDE, and RBU have more avoided O3-related deaths from reducing foreign emissions than from domestic reductions. For six regional emission reductions, the total avoided extra-regional mortality is estimated as 6000 (−3400, 15 500) deaths per year and 25 100 (8200, 35 800) deaths per year through changes in O3 and PM2.5, respectively. Interregional transport of air pollutants leads to more deaths through changes in PM2.5 than in O3, even though O3 is transported more on interregional scales, since PM2.5 has a stronger influence on mortality. For NAM and EUR, our estimates of avoided mortality from regional and extra-regional emission reductions are comparable to those estimated by regional models for these same experiments. In sectoral emission reductions, TRN emissions account for the greatest fraction (26–53 % of global emission reduction) of O3-related premature deaths in most regions, in agreement with previous studies, except for EAS (58 %) and RBU (38 %) where PIN emissions dominate. In contrast, PIN emission reductions have the greatest fraction (38–78 % of global emission reduction) of PM2.5-related deaths in most regions, except for SAS (45 %) where RES emission dominates, which differs with previous studies in which RES emissions dominate global health impacts. The spread of air pollutant concentration changes across models contributes most to the overall uncertainty in estimated avoided deaths, highlighting the uncertainty in results based on a single model. Despite uncertainties, the health benefits of reduced intercontinental air pollution transport suggest that international cooperation may be desirable to mitigate pollution transported over long distances.