In this study, a high energy planetary ball milling technique was used to synthesize nano-crystalline Mo-Cu alloys. Molybdenum trioxide (MoO3) and copper oxide (CuO) were used as the starting materials. Carbo-thermal co-reduction of mixed Mo and Cu oxides powders was done with milling followed by a heat treatment at a high temperature. Differential thermal analysis/thermogravimetric (DTA/TG) was used to determine the heat treatment temperature of activated powders. X-ray diffraction (XRD) analysis was used to investigate the phase structure during the milling and heat treatment. Field emission scanning electron microscopy (FESEM) has been employed to investigate the morphology of powder particles. It was found that the complete carbo-thermal reduction of the oxides mixture may not be possible by the mechanical milling at the ambient temperature and based on thermodynamic investigations, thermal activation was necessary to reduce a MoO3-CuO mixture to a metallic structure. Some peaks at 400, 600 and 950 °C from DTG results of the mixture sample milled for 10 h were observed which were related to the Cu6Mo5O18, MoO2-Cu and Mo formation during carbo-thermal reduction of the MoO3-CuO mixture, respectively. XRD results showed 10 h milled sample after reduction at 1000 °C contained nano-crystalline Mo-Cu alloys with a mean crystallite size of 42 nm for Mo and 37 nm for Cu calculated by the Scherrer equation.