To address the issue of processing deformation at the bottom of grooves during discontinuous slot milling of large thin-walled components—caused by their weak rigidity and uneven wall thickness, which impacts processing accuracy—a comprehensive compensation method for processing deformation errors is proposed. Initially, a milling force measurement experiment is conducted using empirical methods. Through regression analysis, a mapping relationship between processing parameters and milling forces is established, and a milling force prediction model is created. To overcome the low simulation calculation efficiency for large thin-walled components, the equivalent stiffness theory is applied to simplify the deformation region. An improved substructure simulation method is then introduced by replacing the main structure to simulate multi-layer milling processes. Combined with the milling force prediction model, this method predicts processing deformation with a 27.27% improvement in calculation efficiency compared to the full-structure finite element method. Next, using an in-machine measurement system to collect wall thickness data at the groove bottom, a deformation correction model is developed. The predicted processing deformation is corrected by applying inter-layer and node correction coefficients. The inter-layer correction coefficients are iteratively calculated using the secant method, and discrete compensation points are fitted to the machining path using non-uniform rational B-splines. Finally, an in-machine measurement system tailored for the robotic milling of large thin-walled components is designed and implemented. Comparative experiments on milling processing error compensation are conducted. Experimental results demonstrate that, after applying the comprehensive compensation method, processing error is reduced by 92.09% and 77.63% compared to no compensation and the mirror iterative compensation method, respectively. These findings validate the effectiveness of the proposed comprehensive compensation approach for processing deformation errors.