The urban heat island effect (UHI) has been widely observed globally, causing climate, health, and energy impacts in cities. The UHI intensities have been found to largely depend on background climate and the properties of the urban fabric. Yet, a complete mechanistic understanding of how UHIs develop at a global scale is still missing. Using an urban ecohydrological and land-surface model (urban Tethys-Chloris) in combination with multi-source remote sensing data, we performed simulations for 49 large urban clusters across the Northern Hemisphere in 2009–2019 and analysed how surface and canopy air UHIs (SUHI and CUHI, respectively) develop during day and night. Biophysical drivers triggering the development of SUHIs and CUHIs have similar dependencies on background climate, but with different magnitudes. In humid regions daytime UHIs can be largely explained by the urban-rural difference in evapotranspiration, whereas heat convection and conduction are important in arid areas. Plant irrigation can largely promote daytime urban evapotranspiration only in arid and semi-arid climates. During night, heat conduction from the urban fabric to the environment creates large UHIs mostly in warm arid regions. Overall, this study presents a mechanistic quantification of how UHIs develop worldwide and proposes viable solutions for sustainable climate-sensitive mitigation strategies.