Globally, malaria cases have drastically dropped in recent years. However, a high incidence of malaria remains in some sub-Saharan African countries. South Africa is mostly malaria-free, but northeastern provinces continue to experience seasonal outbreaks. Here we investigate the association between malaria incidence and spatio-temporal climate variations in Limpopo. First, dominant spatial patterns in malaria incidence anomalies were identified using self-organizing maps. Composite analysis found significant associations among incidence anomalies and climate patterns. A high incidence of malaria during the pre-peak season (Sep-Nov) was associated with the climate phenomenon La Niña and cool air temperatures over southern Africa. There was also high precipitation over neighbouring countries two to six months prior to malaria incidence. During the peak season (Dec-Feb), high incidence was associated with positive phase of Indian Ocean Subtropical Dipole. Warm temperatures and high precipitation in neighbouring countries were also observed two months prior to increased malaria incidence. This lagged association between regional climate and malaria incidence suggests that in areas at high risk for malaria, such as Limpopo, management plans should consider not only local climate patterns but those of neighbouring countries as well. These findings highlight the need to strengthen cross-border control of malaria to minimize its spread.