This paper examines the impact of climate change on children’s health, in the Limpopo Province of South Africa. Twenty one years climatic data were collected to analyse climatic conditions in the province. The study also employs 12 years hospital records of clinically diagnosed climate-related ailments among children under 13 years to examine the incidence, spatio-temporal, age and sex variations of the diseases. Regression analysis was employed to examine the relationships between climatic parameters and incidence of diseases and also to predict distribution of disease by 2050. The results show that the most prevalent diseases were diarrhea (42.4%), followed by respiratory infection (31.3%), asthma (6.6%) and malaria (6.5%). The incidence varied within city, with the high density areas recording the highest proportion (76.7%), followed by the medium (9.4%) and low (2.5%) density residential areas. The most tropical location, Mussina, had the highest incidence of the most prevalent disease, diarrhea, with 59.4%. Mortality rate was higher for males (54.2%). Analysis of 21 years of climatic data show that maximum temperature is positively correlated with years in four cities with r coefficients of 0.50; 0.56, 0.48 and 0.02, thereby indicating local warming. Similarly rainfall decreased over time in all the cities, with r ranging from −0.02 for Bela Bela to r = 0.18 for Makhado. Results of the regression analysis show that 37.9% of disease incidence is accounted for by the combined influence of temperature and rainfall.