Study on mechanics of milling of thin-wall components using a helical end mill is important in view of its complex nature and prominent applications in aerospace, automobile and electronics areas. This article presents a realistic three-dimensional, thermo-structural, finite-element-based mathematical model for thin-wall milling of aerospace grade aluminum alloy. Lagrangian formulation with explicit solution scheme was employed to simulate the interaction between helical milling cutter and the workpiece. Behavior of the material at high strain, strain rate and temperature was defined by Johnson–Cook material constitutive model. Johnson–Cook damage law and friction law were used to account for chip separation and contact interaction. Experimental work was carried out to validate the results predicted by the mathematical model. The developed model predicted the forces in radial, feed and axial directions with errors of 14%, 26% and 33%, respectively. The prediction errors for deflections at top, middle and bottom portions of thin wall were within 11%–39%. The simulated chip dimensions were in good agreement with experimental results while the computed cutting temperature varied by 17% with respect to the experimental value. Overall, it was found that the developed model predicts the process responses with fair and acceptable prediction accuracy. Using the developed model, a study on the effect of process parameters on the performance parameters, namely cutting and thrust forces, stress distribution, cutting temperature, part deflection and chip morphology was carried out, which is not possible using a two-dimensional orthogonal or oblique cutting model. It was found that the developed three-dimensional mathematical model provided very useful insights into the complex physical interaction of helical cutting tool and workpiece during thin-wall milling of aerospace alloys.