In this work, we report a comprehensive investigation on mechanical and giant magneto-impedance (GMI) properties of melt-extracted Co-rich amorphous microwires with the nominal composition of Co69.25Fe4.25Si13B13.5−xNbx (x = 0, 1, 2, 3, 4). Results show that the tensile strength and GMI properties gradually increase with the substitution of B by Nb at first, and then decrease with a further Nb substitution. The melt-extracted microwires with the substitution of B by 3% Nb exhibit a maximum tensile strength σm of 4000 ± 50 MPa owing to the formation of nanosized crystals in the amorphous matrix. In addition, the substitution of B by 1% Nb assures an excellent GMI property. At 5 MHz, the maximum GMI ratio [ΔZ/Zmax]max for the melt-extracted microwires reaches as high as 450 ± 10% versus 380 ± 10% for traditional CoFeSiB microwires and the field-response sensitivity increases from 350 ± 10% Oe−1 to 700 ± 10% Oe−1 for 1% Nb substitution. It is thus concluded that both mechanical and GMI properties of the melt-extracted Co-based amorphous microwires can be greatly improved by properly adding Nb, and this is promising for many engineering applications, including high-resolution magnetic, stress and biomedical sensors.