In this study, Python Surface Energy Balance System (PySEBS) software was developed in the Python 2.7 programming language for continuous calculation of actual evapotranspiration (ET_a) at regional scales. The software is based on the Surface Energy Balance System (SEBS) model, which uses basic meteorological data, MODIS remote sensing data, and Digital Elevation Model (DEM) data as the original input data and finally outputs daily-scale ET_a in the form of raster data with a spatial resolution of 1 km × 1 km. To verify the reliability of the PySEBS model, the ET_a of spring maize during the growing season in Jilin Province, China, from 2001 to 2020 was calculated and analyzed in this study and compared with the results of similar studies by others. The findings showed that the PySEBS model has a reasonable accuracy in estimating ET_a within ±15% and is a robust model that can achieve the continuous calculation of ET_a at a regional scale. Therefore, PySEBS software is a useful tool for regional irrigation scheduling and water resources management.