This paper systematically reports the thermodynamic characteristic and phase evolution of immiscible Cr-Mo binary alloy during mechanical alloying (MA) process. The Cr-35Mo (in at%) powder mixture was milled at 243 and 258 K, respectively, for different time. For comparative study, Cr-15Mo and Cr-62Mo powder mixtures were milled at 243 K for 18 h. Solid solution Cr(Mo) with body-centered cubic (bcc) crystal structure and amorphous Cr(Mo) alloy was obtained during MA process caused by high-energy ball milling. Based on the Miedema's model, the free-energy change for forming either a solid solution or an amorphous in Cr-Mo alloy system is positive but small at a temperature range between 200 and 300 K. The thermodynamical barrier for forming alloy in Cr-Mo system can be overcome when MA occurs at 243 K, and the supersaturated solid solution crystal nuclei with bcc structure form continually, and three supersaturated solid solutions of Cr-62Mo, Cr-35Mo and Cr-15Mo formed. Milling the Cr-35Mo powder mixture at 258 K, the solid solution Cr(Mo) forms firstly, and then the solid solution Cr(Mo) transforms into the amorphous Cr(Mo) alloy with a few of nanocrystallines when milling is prolonged. At higher milling temperature, it is favorable for the formation of the amorphous phase, as indicated by the thermodynamical calculation for immiscible Cr-Mo alloy system.