Variations in urban form lead to the development of distinctive intra-urban surface thermal patterns. Previous assessment of the relation between urban structure and satellite-based Land Surface Temperature (LST) has generally been limited to single-city cases. Here, examining 25 European cities (June–August 2017), we estimated the statistical association between surface parameters—the impervious fraction (λimp), the building fraction (λb), and the building height (H)—and the neighborhood scale (1000 × 1000 m) LST variations, as captured by the Moderate Resolution Imaging Spectroradiometer (MODIS) sensor. Correlation analysis, multiple linear regression, and spatial regression were used. As expected, λimp had a consistent positive influence on LSTs. In contrast, the relation of LST with λb and H was generally weaker or negative in the daytime, whereas at night it shifted to a robust positive effect. In particular, daytime LSTs of densely built, high-rise European districts tended to have lower values. This was especially the case for the city of Athens, Greece, where a more focused analysis was conducted, using further surface parameters and the Local Climate Zone (LCZ) scheme. For the urban core of the city, the canyon aspect ratio H/W had a statistically significant (p <0.01) negative relationship with LST by day (Spearman’s rho = −0.68) and positive during nighttime (rho = 0.45). The prevailing intra-urban surface thermal variability in Athens was well reproduced by a 5-day numerical experiment using the meteorological Weather Research and Forecasting Model (WRF) model and a modified urban parameterization scheme. Although the simulation resulted in some systematic errors, the overall accuracy of the model was adequate, regarding the surface temperature (RMSE = 2.4 K) and the near-surface air temperature (RMSE = 1.7 K) estimations.