Numerous studies on the association between the human development index (HDI) and road traffic death rate (RTDR) merely focus on developed countries, not reflecting the relationship between the HDI components and RTDR in a time-trend analysis. Accordingly, this study analyzes the trends of RTDR and their association with the HDI and its components from 2000 to 2019. The RTDR data of 154 countries were imported into the unconditional latent growth model (LGM) to assess the RTDR trends. The impact of the HDI and its components (viz., education, income, and life expectancy [LE viz]) on the trajectory of RTDR was also evaluated using the conditional LGM. The results of the unconditional LGM indicated an overall decreasing trend in RTDR. The conditional LGM results revealed the negative effect of the HDI and its components on the model parameters. The findings of random forests indicated that education and LE were the most crucial variables. Overall, this study emphasizes the significance of HDI and its components, particularly education and LE, in lowering the number of traffic fatalities. In this sense, improving formal education and LE could be one of the main policies that policymakers could consider to reduce RTDR.