Evidence shows a continuing increase in the frequency and severity of global heatwaves^1,2, raising concerns about the future impacts of climate change and the associated socioeconomic costs^3,4. Here we develop a disaster footprint analytical framework by integrating climate, epidemiological and hybrid input–output and computable general equilibrium global trade models to estimate the midcentury socioeconomic impacts of heat stress. We consider health costs related to heat exposure, the value of heat-induced labour productivity loss and indirect losses due to economic disruptions cascading through supply chains. Here we show that the global annual incremental gross domestic product loss increases exponentially from 0.03 ± 0.01 (SSP 245)–0.05 ± 0.03 (SSP 585) percentage points during 2030–2040 to 0.05 ± 0.01–0.15 ± 0.04 percentage points during 2050–2060. By 2060, the expected global economic losses reach a total of 0.6–4.6% with losses attributed to health loss (37–45%), labour productivity loss (18–37%) and indirect loss (12–43%) under different shared socioeconomic pathways. Small- and medium-sized developing countries suffer disproportionately from higher health loss in South-Central Africa (2.1 to 4.0 times above global average) and labour productivity loss in West Africa and Southeast Asia (2.0–3.3 times above global average). The supply-chain disruption effects are much more widespread with strong hit to those manufacturing-heavy countries such as China and the USA, leading to soaring economic losses of 2.7 ± 0.7% and 1.8 ± 0.5%, respectively.