Amyloid β (Aβ) fibrils are a pathological hallmark of Alzheimer’s disease and are stabilized by highly ordered β-sheet stacking and dense hydrogen-bond networks, which confer exceptional mechanical rigidity. Recently, external electric fields (EFs) have attracted attention as a non-invasive physical stimulus capable of modulating biomolecular assemblies; however, the residue-level mechanisms governing EF-induced destabilization of amyloid fibrils remain largely unexplored. Here, we employ all-atom molecular dynamics (MD) simulations combined with electric-field MD (EF-MD) and steered MD (SMD) to investigate the electromechanical response of Aβ fibrils with targeted mutations at Lysine 16 (K16), a key residue mediating electrostatic interactions and β-sheet packing. Two contrasting mutations were introduced: a charge-reversal mutation (K16D) and a bulky aromatic mutation (K16W). Uniform electric fields were applied along three orthogonal directions to probe directional dependence and mutation-specific responses. Prior to EF application, SMD tensile tests yielded Young’s moduli in the range of 3.4–3.9 GPa for both wild-type and mutant fibrils, consistent with experimentally reported values. EF exposure induced progressive disruption of β-sheet alignment and hydrogen-bond networks, leading to pronounced mechanical softening. Under EF conditions, the Young’s modulus decreased to 0.5–0.8 GPa in the longitudinal pulling direction and further declined to the tens-of-megapascal range (10–70 MPa) in the transverse direction, corresponding to an overall stiffness reduction of 85–95%. The charge-reversal mutation exhibited strong direction-dependent vulnerability, whereas the bulky aromatic mutation displayed comparatively isotropic resistance to EF-induced perturbations. Post-field recovery simulations demonstrated that EF-induced damage is largely irreversible, with persistent expansion of solvent-accessible regions and sustained loss of mechanical rigidity. Overall, this study elucidates a residue-specific electromechanical coupling mechanism in amyloid fibrils, showing how local electrostatics and steric constraints govern EF sensitivity, structural anisotropy, and mechanical failure. These findings suggest that electric fields may serve as a promising physical strategy to destabilize amyloid assemblies and enhance therapeutic accessibility.