Infant mortality rate (IMR) is a crucial indicator of healthcare performance and a reflection of a country’s socioeconomic development. We analyzed the trends of IMR in Central Asia (CA) countries and its determinants in Kazakhstan, which is a middle-income country. Linear regression was used for IMR trend analysis in CA countries from 2000 to 2020 and for exploring associations between IMR and socioeconomic factors, health service-related factors, and population health indicators-related factors. A gamma generalized linear model was applied to define associations with various determinants. Our analysis revealed that IMR has decreased in all CA countries, with Kazakhstan having the lowest rate in 2000 and 2020. Our results suggest that socioeconomic indicators, such as total unemployment, Gini index, current health expenditure, gross domestic product (GDP), proportion of people living in poverty, and births by 15–19-year-old mothers, were associated with increased infant mortality rates. Improving socioeconomic conditions, investing in healthcare systems, reducing poverty and income inequality, and improving access to education, are all potential issues for further development. Addressing these factors may be critical for improving maternal and child health outcomes in the region.