To address the challenges associated with fatigue damage monitoring in load-bearing composite structures, we developed a method that utilizes Lamb wave propagation and partial least squares regression (PLSR) for effective monitoring. Initially, we extracted diverse characteristics from both the time and frequency domains of the Lamb wave signal to capture the essence of the damage. Subsequently, we constructed a PLSR model, leveraging Lamb wave multi-feature fusion, specifically tailored for in-service fatigue damage monitoring. The efficacy of our proposed approach in quantitatively monitoring fatigue damage was thoroughly validated through rigorous standard fatigue tests. In practical applications, our model effectively mitigated the impact of multicollinearity among feature variables on model accuracy. Furthermore, the PLSR model demonstrated superior accuracy compared to the PCR model, given an equal number of principal components. To strike a harmonious balance between efficiency and precision, we optimized the size of the feature variable. The results show that the optimized PLSR model achieved an R-squared value exceeding 97% in predicting the in-service damage area. This underscores the robustness and reliability of our method in accurately monitoring fatigue damage in load-bearing composite structures.