Ghana’s savannah ecosystem has been subjected to a number of climatic hazards of varying severity. This paper presents a spatial, time-series analysis of the impacts of multiple hazards on the ecosystem and human livelihoods over the period 1983–2012, using the Upper East Region of Ghana as a case study. Our aim is to understand the nature of hazards (their frequency, magnitude and duration) and how they cumulatively affect humans. Primary data were collected using questionnaires, focus group discussions, in-depth interviews and personal observations. Secondary data were collected from documents and reports. Calculations of the standard precipitation index (SPI) and crop failure index used rainfall data from 4 weather stations (Manga, Binduri, Vea and Navrongo) and crop yield data of 5 major crops (maize, sorghum, millet, rice and groundnuts) respectively. Temperature and windstorms were analysed from the observed weather data. We found that temperatures were consistently high and increasing. From the SPI, drought frequency varied spatially from 9 at Binduri to 13 occurrences at Vea; dry spells occurred at least twice every year and floods occurred about 6 times on average, with slight spatial variations, during 1988–2012, a period with consistent data from all stations. Impacts from each hazard varied spatio-temporally. Within the study period, more 70% of years recorded severe crop losses with greater impacts when droughts and floods occur in the same year, especially in low lying areas. The effects of crop losses were higher in districts with no/little irrigation (Talensi, Nabdam, Garu-Tempane, Kassena-Nankana East). Frequency and severity of diseases and sicknesses such as cerebrospinal meningitis, heat rashes, headaches and malaria related to both dry and wet conditions have increased steadily over time. Other impacts recorded with spatio-temporal variations included destruction to housing, displacement, injury and death of people. These impacts also interacted. For example, sicknesses affected labour output; crop losses were blamed for high malnutrition; and reconstruction of properties demanded financial resources largely from sale of agricultural produce. These frequent impacts and their interactions greatly explain the persistent poverty in the area.