With the development of remote sensing technology, the estimation of the chlorophyll content (CHLC) of vegetation via satellite data has become an important means of monitoring vegetation health, and high-precision estimation has been the focus of research in this field. In this study, we used larch affected by Yarl’s larch looper (Erannis jacobsoni Djak) in the boundary region of Mongolia as the research object, simulated the multispectral reflectance, downscaled Sentinel-2A satellite data, performed mixed-pixel decomposition, analyzed the potential of Sentinel-2A satellite data for estimating the chlorophyll content by calculating the spectral indices (SIs) and spectral derivatives (SDFs) of images, and then extracted sensitive spectral features as the model training set. Spectral features sensitive to the chlorophyll content were extracted to establish the training set, and, finally, the chlorophyll content estimation model for larch was constructed on the basis of the partial least squares algorithm (PLSR). The results revealed that SI and SDF based on simulated remote sensing data were highly sensitive to the chlorophyll content under the influence of pests, with the SAVI and EVI2 spectral indices as well as the D_B2 and D_B5 spectral derivatives being the most sensitive to the chlorophyll content. The estimation models based on simulated data performed significantly better than models without simulated data in terms of accuracy, especially those based on SDF-PLSR. The simulated spectral reflectance well reflected the spectral characteristics of the larch canopy and was sensitive to damaged larch, especially in the green light, red edge, and near-infrared bands. The proposed approach improves the accuracy of chlorophyll content estimation via Sentinel-2A data and enhances the ability to monitor changes in the chlorophyll content under complex forest conditions through simulations, providing new technical means and a theoretical basis for forestry pest monitoring and vegetation health management.