Urban thermal anisotropy (UTA) drastically impacts satellite-derived urban surface temperatures and fluxes, and consequently makes it difficult to gain a more comprehensive understanding of global urban climates. However, UTA patterns and associated biases in observed urban climate variables have not been investigated across an adequate number of global cities with diverse contexts; nor is it known whether there are globally measurable factors that are closely related to the UTA intensity (UTAI, quantified as the maximum difference between the nadir and off-nadir urban thermal radiation). Here we investigate the UTAI over more than 5500 cities worldwide using multi-angle land surface temperature (LST) observations from 2003 to 2021 provided by Moderate Resolution Imaging Spectroradiometer (MODIS). The results show that the global mean UTAI can reach 5.1, 2.7, 2.4, and 1.7 K during summer daytime, winter daytime, summer nighttime, and winter nighttime, respectively. Using nadir LST observations as a reference, our analysis reveals that UTA can lead to an underestimation of satellite-based urban surface sensible heat fluxes (H) by 45.4% and surface urban heat island intensity (Is) by 43.0% when using LST observations obtained from sensor viewing zenith angles (VZAs) of ±60°. Practitioners can limit the biases of H and Is within ±10% by using LSTs from sensor VZAs within ±30°. We also find that UTAI is closely related to urban impervious surface percentage and surface air temperature across global cities. These findings have implications for angular normalization of satellite-retrieved instantaneous LST observations across cities worldwide.