This study numerically simulated and experimentally validated the interaction between a nanosecond pulse fiber laser and an Al2O3-based ceramic material. COMSOL Multiphysics 6.1 software was used to investigate the thermal process and select optimal parameters. The Al2O3-based ceramic is a pivotal component in parts and cutting tools and exhibits excellent wear resistance, particularly in semiconductor and medical fields. A simulated laser beam utilizes the primary parameters of pulse width, repetition frequency, energy distribution, and dimensions of the laser convergence region. The moving beam, which is characterized by its scanning rate, traverses along the Al2O3 material surface. The processing mechanism is significantly influenced and defined by the material’s thermodynamic parameters and the parameters of the laser beam. To assess the processing capabilities and to optimize the parameters of the laser processing system, two-dimensional thermal-affected zones were evaluated following each scanning cycle. The simulation results provide insights into the selection of optimal laser source parameters for experimental processing. The optimal parameters derived from the simulation were experimentally verified for the Al2O3-based ceramic samples.