Despite a substantial number of COVID-19 related research papers published, it remains unclear as to which factors are associated with the observed variation in global transmission and what are their relative levels of importance. This study applies a rigorous statistical framework to provide robust estimations of the factor effects for a global and integrated perspective on this issue. We developed a mixed effect model exploring the relative importance of potential factors driving COVID-19 transmission while incorporating spatial and temporal heterogeneity of spread. We use an integrated data set for 87 countries across six continents for model specification and fitting. The best model accounts for 70.4% of the variance in the data analyzed: 10 fixed effect factors explain 20.5% of the variance, random temporal and spatial effects account for 50% of the variance. The fixed effect factors are classified into climatic, demographic and disease control groups. The explained variance in global transmission by the three groups are 0.6%, 1.1%, and 4.4% respectively. The high proportion of variance accounted for by random effects indicated striking differences in temporal transmission trajectories and effects of population mobility among the countries. In particular, the country-specific mobility-transmission relationship turns out to be the most important factor in explaining the observed global variation of transmission in the early phase of COVID-19 pandemic. Plain Language Summary We have observed substantial variation in global transmission trajectories of COVID-19. Using statistical analysis, this study aims to investigate the factors that are associated with the observed variation in global transmission and what are their relative levels of importance. We conclude that the variation in transmission trajectories in various countries is mostly accounted for by spatiotemporal heterogeneity in transmission. In particular, disease control policies and population response to COVID-19 transmission make the largest contribution and demographic features have the least importance. Climatic factors also play a role but turn to be much less important than disease control policies. The mobility-transmission relationship is country-specific and turns out to be the most important factor in explaining the observed global variation of transmission. The complexity of COVID-19 transmission is also demonstrated through the wide range of estimated effects of population mobility on transmission between countries.