There has been a rising trend of labor migration globally. Given their alien status within the legal framework of the host countries, migrant domestic workers (MDWs) are especially vulnerable to poor employment conditions that may affect their health status, yet there is still a lack of quantitative evidence in this population hitherto. Using randomly sampled data from a cross-sectional survey of 2,017 live-in female MDWs in Hong Kong, a setting with a high concentration of MDWs, this study examined the association of employment conditions with physical and mental health among the MDWs. We observed poorer physical and mental health status among the MDWs when compared with the general population in Hong Kong. Our findings suggest that employment conditions, including household size, working on the rest day, and housing type, and age were associated with physical health, while employment conditions, including not ever receiving wages on time, frequency of financial remittances, paying the employment agency, having a private room, fulfillment of work-related needs, physical abuse, and discrimination, and sociodemographic characteristics, including age and duration of migration, were associated with mental health. Social support in general did not confound these associations, but religious activities and daily contact with friends were also associated with mental health. Our findings have important implications in designing interventions and policies to improve the physical and mental well-being of this vulnerable migrant population.