BACKGROUND: Air pollution is the sixth highest risk factor for attributable disability-adjusted life-years (DALYs) in North Africa and the Middle East, but the relative importance of different subtypes of air pollution and any potential differences in their health effects by population demographics or country-level socioeconomic factors have not been fully explored. The objective of this study was to investigate the effect of high ambient particulate matter less than 2·5 μm in size (PM) and ambient ozone air pollution on disease burden, mortality, and life expectancy in 21 countries in the North Africa and the Middle East super-region from 1990 to 2019 using the Global Burden of Diseases, Injuries, and Risk Factors (GBD) Study estimates. METHODS: The study data were derived from GBD 2019, examining data from 1999 to 2019 in North Africa and the Middle East. In this study, the types of air pollution investigated included PM pollution and ambient ozone pollution. PM pollution itself was categorised as household air pollution from solid fuels and ambient PM pollution. The burden attributable to each risk factor, directly or indirectly, was incorporated in the population attributable fraction to estimate the total attributable deaths and DALYs. The summary exposure value (SEV) as the relative risk-weighted prevalence of exposure was extracted to compare the distribution of excess risk times the exposure level in a population where everyone is at maximum risk and ranges from zero (no excess risk exists in a population) to 100 (highest risk). The effect of air pollution on life expectancy was estimated via a cause-deleted life table analysis. FINDINGS: The age-standardised DALYs rate attributable to air pollution declined by 44·5%, from 4884·2 (95% uncertainty interval 4381·5-5555·4) to 2710·4 (2317·3-3125·6) per 100 000 from 1990 to 2019. Afghanistan (6992·3, 5627·7-8482·7), Yemen (4212·4, 3241·3-5418·1), and Egypt (4034·8, 3027·7-5138·6) had the highest age-standardised DALYs rates attributable to air pollution in 2019 per 100 000, whereas Türkiye (1329·2, 1033·7-1654·7), Jordan (1447·3, 1154·2-1758·5), and Iran (1603·0, 1404·7-1813·8) had the lowest rates. During the study period, the age-standardised SEV of air pollution (PM and ambient ozone in total) decreased by 10·9% (5·8-17·7%) in the super-region, whereas the SEV of ambient ozone pollution alone increased by 7·7% (0·7-14·3%). Among the components of PM pollution, the SEV of ambient PM pollution increased by 40·1% (25·2-63·7%); however, the SEV of household air pollution from solid fuels decreased by 70·6% (64·1-77·0%). Among the investigated types of air pollution, 98·9% of the DALYs from air pollution in the super-region were attributable to PM pollution. If air pollution had been lowered to the theoretical minimum risk exposure levels for 2019, then the average life expectancy would have been 1·6 years higher. INTERPRETATION: The burden attributable to air pollution substantially decreased in the study period across the super-region as a whole. Most of the burden from air pollution is attributed to PM pollution, the exposure to which has substantially increased in the past three decades. Interventions and policies that reduce population exposure to PM pollution could potentially increase the average life expectancy in the super-region. This finding calls for concerted efforts from governments and public health authorities in the super-region to tackle air pollution as an important threat to population health. FUNDING: Bill & Melinda Gates Foundation.