Exploring the spatio-temporal variations of COVID-19 transmission and its potential determinants could provide a deeper understanding of the dynamics of disease spread. This study aimed to investigate the spatio-temporal spread of COVID-19 infections in England, and examine its associations with socioeconomic, demographic and environmental risk factors. We obtained weekly reported COVID-19 cases from 7 March 2020 to 26 March 2022 at Middle Layer Super Output Area (MSOA) level in mainland England from publicly available datasets. With these data, we conducted an ecological study to predict the COVID-19 infection risk and identify its associations with socioeconomic, demographic and environmental risk factors using a Bayesian hierarchical spatio-temporal model. The Bayesian model outperformed the ordinary least squares model and geographically weighted regression model in terms of prediction accuracy. The spread of COVID-19 infections over space and time was heterogeneous. Hotspots of infection risk exhibited inconsistent clustering patterns over time. Risk factors found to be positively associated with COVID-19 infection risk were: annual household income [relative risk (RR) = 1.0008, 95% Credible Interval (CI) 1.0005–1.0012], unemployment rate [RR = 1.0027, 95% CI 1.0024–1.0030], population density on the log scale [RR = 1.0146, 95% CI 1.0129–1.0164], percentage of Caribbean population [RR = 1.0022, 95% CI 1.0009–1.0036], percentage of adults aged 45–64 years old [RR = 1.0031, 95% CI 1.0024–1.0039], and particulate matter ($$\text {PM}_{2.5}$$
PM
2.5
) concentrations [RR = 1.0126, 95% CI 1.0083–1.0167]. The study highlights the importance of considering socioeconomic, demographic, and environmental factors in analysing the spatio-temporal variations of COVID-19 infections in England. The findings could assist policymakers in developing tailored public health interventions at a localised level.