In the 1960s, Lake Chad (LC) was one of the largest inland water body on the earth and since then, it has extremely shrunk from a surface area of 25,000 km2 to 2000 km2. The present study determines hydro-climatic changes in the active parts of the Lake Chad basin by using trend analysis and the causes of declining stream flow to LC due to human interventions and climate variability by using a hydrological approach. One approach, which is used to estimate changes in stream flow due to climate variability, is also modified in this study. Trend results showed that mean temperature exhibited very strong increasing trends, with a mean rise of 1.4 °C for 1951–2015, while precipitation presented very weak to strong declining trends, with an overall decline of 15%. Regarding stream flow, all major rivers showed very strong downward trends, resulting in 67% decline. The northern and eastern regions were the most impacted areas in the basin regarding decreasing precipitation and increasing temperature. The hydrological approach showed that decreasing stream flow to LC varied between 34% and 45% in different decades. In general, human activities attributed a 66% decline in stream flow and climate variability 34% for the impacted period (1972–2013) relative to 1951–1971. Only during 1982–1991, climate variability caused most reduction (59% of total) in stream flow because of devastating drought during this period. Since stream flow to LC was mostly affected by human activities, proper water resources planning and sustainable management are necessary but under the umbrella of considering changing climate. Display omitted •Impacts of climate variability and human activities were assessed using hydrologic approach.•Human activities caused more reduction (66%) in inflow to Lake Chad than climate variability.•Climate variability was assesses using Mann-Kendal and Sen's slope methods.•Highly significant increasing trends were observed, with an increase of 1.4 °C/65 yrs.•Moderate signals of decreasing trends were explored, with decline of 15%/65 yrs.