The COVID-19 pandemic is one of the greatest health challenges humanity has faced in the 21st century. Ghana recorded its first cases on 12 March 2020 and has since implemented several response activities. The incidences and mortalities and their impact on the limited resources require a system to prompt health professionals for early response. Spatio-temporal statistical modelling is essential to understand these dynamics, but it is still lacking implementation in developing countries, especially Ghana. This dataset collection provides district-level data describing the epidemiological progression of COVID-19, associated demographic characteristics, and climatic variables across Ghana between March 2020 and February 2022. The datasets were used in multiple peer-reviewed studies examining spatiotemporal dynamics, climatic influences, and epidemiological modeling of COVID-19 trends in Ghana