Crystal orientation and thermal effect are critical factors that govern the machining performance of γ-TiAl alloy during laser-assisted diamond turning (LADT). However, the underlying mechanism by which their synergistic interaction influences microstructural evolution and cutting behavior remains insufficiently understood. Therefore, the present study developed an LADT model based on molecular dynamics (MD) simulations to systematically investigate how the combined effects of crystal orientation and thermal input influence the microstructural evolution of single-crystal γ-TiAl alloy, as well as its implications for plastic deformation, mechanical response, and tool wear. Results indicate that the (110)[11-0]" role="presentation"> [1 1 - 0] crystal orientation, characterized by relatively weak atomic bonding and enhanced dislocation slip capacity, achieves a favorable synergistic interaction with thermal effects, thereby demonstrating superior cutting performance. Enhancing the laser thermal effect effectively reduces the depth of plastic deformation and enhances the material removal rate for the (111)[1-10]" role="presentation"> [ 1 - 10] orientation, whereas the opposite trend is observed for the (001)[1-1-0]" role="presentation"> [ 1 - 1 - 0] orientation. Regarding chip morphology, the application of laser energy promotes the occurrence of adiabatic shear under both the (001)[1-1-0]" role="presentation"> [ 1 - 1 - 0] and (111)[1-10]" role="presentation"> [ 1 - 10] orientations, leading to increased chip serration. When the thermal effect is intensified to the point of inducing significant amorphization within the shear zone, the friction coefficient becomes markedly less sensitive to crystallographic anisotropy. Furthermore, the thermal accumulation associated with laser assistance exacerbates amorphous wear on the rake face. These findings offer novel insights into how thermal effects and crystal orientations jointly influence the micro-deformation mechanisms and cutting behavior of nanoscale single-crystal alloys.