Malaria has a significant impact on the lives of many in Ghana. It is one of the key causes of mortality and morbidity, resulting in 32.5% of outpatient visits and 48.8% of under 5-year-old hospital admissions. Future climate change may impact on this risk. This study aims at estimating the impact of climate variables and health facilities on malaria prevalence in Ghana using regional data from January 2012 to May 2017. This study links data at a regional level on malaria cases with weather data to evaluate the impact that changes in weather may have on malaria prevalence in Ghana. The results of fixed-effect modelling show that the maximum temperature has a statistically significant negative impact on malaria in the context of Ghana, and rainfall with a lag of two months has a positive statistically significant impact. Adapting to climate change in Ghana requires a better understanding of the climate-malaria relationship and this paper attempts to bridge this gap.