Shallow water benthic habitats have been significantly degraded and seriously threatened by intensifying climate changes and anthropogenic stressors. Benthic reflectance (Rbλ) of optically shallow waters (OSWs) is a key parameter for remote sensing of benthic habitats’ composition and health status. The remote sensing reflectance (Rrsλ) just above the water surface contains the coupled spectral information of the water column and seabed in OSWs, which makes our effort challenging to separate the signals between seabed and water column properties. Due to too many unknowns of the water column and seabed optical properties, the current approaches are inaccurate or inadequate to retrieve benthic reflectance spectra over a large area from remotely sensed data. In this study, we proposed an enhanced large-scale benthic reflectance (LSBR) retrieval model from satellite data in OSWs with only input of Rrsλ. A new spectral library of benthic reflectance was built upon multi-source reflectance datasets obtained from several open-source field measurements. Then, the specific relationship between Rb443nm and Rb490nm was developed. By combining a semi-analytical benthic reflectance (SABR) model based on radiative transfer simulations and this relationship, water-column chlorophyll concentration (chl) was determined. Moreover, large-scale water depth was estimated by Rrsλ through satellite-derived bathymetry (SDB) technologies. Finally, benthic reflectance was retrieved with the inputs of the satellite-derived Rrsλ, chl, and water depth. In this way, the LSBR model fulfills the Rbλ retrieval with only input of satellite-derived Rrsλ. The new model was successfully applied to Sentinel-2/MSI data in the seagrass region of Xincun Bay and the coral region of Huaguang Reef and further verified by using field measurements and results of the along-track benthic reflectance (ATBR) retrieval model, which combined active lidar and passive high-resolution satellite images. Additionally, to gain insights into the long-term evolution of benthic communities, a typical application of the LSBR model for detecting benthic changes was conducted using eight years of Sentinel-2/MSI data in Heron Reef, depicting a similar consistency between the probable deterioration and restoration region and the sea surface temperature (SST) anomalies. The results demonstrated the robustness and accuracy of the LSBR model in retrieving benthic reflectance at large scales. The LSBR model should be helpful for further investigating benthic changes which can enhance the ability to monitor and assess the health status of submerged ecosystems in OSWs.