Abstract The semi-arid ecosystems dominate the inter-annual variability of the global carbon sink and the driving role of semi-arid ecosystems is becoming increasingly important. However, the impacts of climate change on the dynamics of carbon and water fluxes in global semi-arid ecosystems are still not well understood. We used a data-driven (or machine learning) approach, along with observations from a number of FLUXNET sites and spatially continuous satellite and meteorological data, to generate gridded carbon and water flux estimates for semi-arid regions globally, and then examined the magnitude, spatial patterns, and trends of carbon and water fluxes and their responses to climate change during the period 1982–2015. The average annual gross primary productivity (GPP), net ecosystem productivity (NEP), evapotranspiration (ET), and water use efficiency (WUE) were 628.6 g C m⁻² yr⁻¹, 9.6 g C m⁻² yr⁻¹, 463.1 mm yr⁻¹, and 1.60 g C Kg⁻¹ H₂O, respectively. The climate conditions during the period 1982–2015 enhanced gross and net carbon uptake in global semi-arid regions. The spatially-averaged annual GPP, NEP, ET, and WUE in semi-arid regions showed significant increases both globally and regionally (Asia, Africa, and Australia). As with GPP and ET, WUE significantly increased in North America, Asia, Africa, and Australia. Australia was the most sensitive semi-arid region in terms of changes in carbon and water fluxes and their responses to climate. Semi-arid forests, shrublands, and savannas were net carbon sinks; croplands were minor carbon sources; grasslands were nearly carbon neutral. Overall, precipitation was the most important climate factor influencing the carbon and water fluxes; WUE in 40.9% of the semi-arid region was significantly influenced by precipitation. The global climate change is expected to influence global semi-arid ecosystems in many ways and our findings have implications for semi-arid ecosystem management and policy making.