The recent spread of infectious diseases at the pace of extreme weather events as the world's climate changes is becoming worrisome. This study focused on identifying the variation status of observed weather elements and determining their relationship with the pattern of selected diseases in Ondo State, Nigeria. Data on malaria, asthma, typhoid, and pneumonia occurrence were obtained from the Ondo State Specialist Hospital along with temperature (maximum and minimum), rainfall, and relative humidity at the Ondo State Agro-climatological Office between the periods of 2011 and 2021. Descriptive and correlation coefficient statistics were used for data analysis. Results revealed the spread of malaria, asthma, typhoid, and pneumonia as influenced by variations in temperature, rainfall, and relative humidity in the study areas. Malaria exhibited a strong correlation (r > 0.7) with the weather pattern. However, the study showed that malaria and pneumonia were more prevalent than typhoid fever and asthma. The study recommends ameliorating the impacts of observed weather elements on the insurgence of malaria, typhoid, asthma, and pneumonia in the study area through public cautioning strategies on climate adaptation. The public should also be informed of the prevalence of malaria and pneumonia during the months of June, July, and November, along with mitigation measures for sustainable healthy living.