Laser guidance systems are valued for their high precision, long engagement range, and resilience against electronic countermeasures, making them indispensable in modern precision strike operations. However, atmospheric disturbances, especially turbulence-induced wavefront distortions and aerosol-induced extinction attenuation, seriously degrade the optical sensing response and guidance-related measurement accuracy over long distances. Existing studies often examine turbulence or aerosol effects in isolation, without providing a unified framework that links these disturbances directly to seeker optical response metrics. This paper develops a high-fidelity, system-level simulation framework that models the complete process of laser emission, atmospheric propagation, target reflection, and seeker reception. The framework couples multilayer turbulence modeling with altitude-dependent profiles, aerosol extinction and scattering effects derived from MODTRAN data, and wavefront evolution using the angular spectrum method. By directly computing seeker optical response indicators such as angular error, centroid shift, and energy concentration, the model quantitatively evaluates how turbulence strength, aerosol concentration, laser power, and propagation distance interact to affect guidance precision. Validation against representative experimental data demonstrates good agreement and confirms the model’s capability to reproduce the statistical behavior of the measured seeker response. The results further clarify the distinct roles of turbulence-induced phase distortion and aerosol-induced amplitude attenuation, and provide quantitative operating envelopes for laser power and propagation distance. These findings establish both a theoretical foundation and a practical simulation tool to support the optimization of laser-guided weapon systems under complex atmospheric conditions.