© 2021 Elsevier LtdWe report on the mechanical properties of Cu–Nb alloys produced by combinatorial magnetron sputtering. Depending on the composition, the microstructure is either fully amorphous (~30–65 at.% Cu), a dispersion of Cu crystallites in an amorphous matrix (~70 at.%), or a dominant crystalline phase with separated nanoscale amorphous zones (~80 at.% Cu). Nanomechanical probing of the different microstructures reveals that the hardness of the fully amorphous alloy is much higher than a rule of mixture would predict. We further demonstrate a remarkable tunability of the resistance to plastic flow, ranging from ca. 9 GPa in the amorphous regime to ca. 2 GPa in the fully crystalline regime. We rationalize these findings based on fundamental structural considerations, thereby highlighting the vast structure-property design space that this otherwise immiscible binary alloy provides.