The high-temperature stability and mechanical properties of refractory molybdenum alloys are highly desirable for a wide range of critical applications. However, a long-standing problem for these alloys is that they suffer from low ductility and limited formability. Here we report a nanostructuring strategy that achieves Mo alloys with yield strength over 800 MPa and tensile elongation as large as similar to 40% at room temperature. The processing route involves a molecular-level liquid-liquid mixing/doping technique that leads to an optimal microstructure of submicrometre grains with nanometric oxide particles uniformly distributed in the grain interior. Our approach can be readily adapted to large-scale industrial production of ductile Mo alloys that can be extensively processed and shaped at low temperatures. The architecture engineered into such multicomponent alloys offers a general pathway for manufacturing dispersion-strengthened materials with both high strength and ductility.