BACKGROUND: Migrant workers, a population of 170 million, often work in dangerous or unhealthy working environments and are likely to suffer workplace injuries and labour abuses. However, the risk of mortality in migrant workers compared with local workers is unknown. We aim to synthesise global evidence on migrant worker mortality risk and identify social determinants to inform health and safety protections for migrant workers. METHODS: We conducted a systematic review and meta-analysis of peer-reviewed literature to examine mortality outcomes among migrant workers and associated risk factors. We searched MEDLINE, Embase, PsycINFO, and Ovid Global Health for studies published between Jan 1, 2000, and Jan 17, 2023, reporting quantitative primary research in English. A broad definition of migrant worker was used, including any worker who is foreign-born (ie, international first-generation migrant workers), either in paid employment or self-employment. Internal migrants, second-generation migrants, and foreign health-care workers were excluded. The primary outcome was any reported mortality, including all-cause mortality, cause-specific mortality, suicide, homicide, and fatal occupational injury. We used meta-analysis to compare outcomes between migrant worker and local worker populations, and a random-effects model to calculate pooled estimates. We used narrative synthesis to develop a data-driven conceptual framework capturing the intersectional social determinants of mortality in migrant workers. The study protocol is registered on PROSPERO, CRD42023372893. FINDINGS: Of 11 495 identified records, 44 were included in the systematic review, of which 11 studies were pooled in meta-analyses. Data were from 16 countries, most of which were high-income countries, and included 44 338 migrant worker deaths, including migrants from the agriculture, construction, mining, and service industries. Compared with local workers, migrant workers had a higher risk of fatal occupational injury (pooled relative risk 1·71, 95% CI 1·22-2·38; eight studies; I2=99·4%), and a lower risk of all-cause mortality (0·94, 0·88-0·99; three studies, I2=90·7%). Migrant workers were more likely to die from external causes of death (such as falls or assaults) than internal causes of death (such as respiratory or digestive diseases) compared with local workers, with migrant workers also more likely to die from work-related homicides, especially in the retail and sex industries, with some evidence of higher suicide rates among female migrant workers compared with female local workers. Influential social determinants for poor fatality outcomes include migration-related factors (such as lower language proficiency, undocumented status, and long duration of stay) and labour-related factors (such as precarious employment, labour migration policies, and economic deregulation policies). INTERPRETATION: Migrant workers have a higher risk of workplace fatal injury despite being generally healthier than local workers, which could be explained by structural determinants such as precarious employment and inadequate safety protection. This health inequity must be urgently addressed through future interventions that account for migration-related and labour-related social determinants of health at the structural level, such as extending labour protection laws to migrant workers, and improving occupational health and safety and workplace conditions for this vital and growing workforce. FUNDING: UK Medical Research Council and National Institute for Health and Care Research.