The influence of surface microstructural regulation mechanisms on the mechanical and giant magneto-impedance (GMI) properties of as-cast melt-extracted CoFe-based wires has been systematically researched based on morphology, phase distribution and domain structure parameters. A series of statistical models were applied to analyze the mechanical properties and followed by mapping the curve of cumulative failure rate for wire application. It was found that the average and highest fracture strengths, average tensile strain increased with Cu substitution and reached peaks of ~3725 MPa, ~4250 MPa and ~2.7%, respectively. Verified structure-simulation experiments revealed that surface Rayleigh waves effectively split the main crack and the diffusely distributed nanocrystalline in surface area acted as a pinning point to impede the crack growth, enhancing the mechanical properties. The GMI ratio displayed similar variations and attained a maximum value of 700 ± 5% as well as the resistance and reactance ratios improved to ~687% and ~2206%, respectively. The enhanced relative dielectric permeability μs resulting from the increased domain wall energy density and the decreased surface domain width. The unique synchronous enhancement of CoFe-based wires satisfies the demand for emerging magnetoelectric sensor applications, e.g. flexible and wearable sensors, equipment self-monitoring sensors, and array robotic skin sensors under harsh working environments.