Hot deformation of five microstructurally different sintered WC-Co cemented carbides during hot compression testing was investigated in the temperature range of 700–1000 °C and at strain rates ranging from 0.0005 to 0.1 s−1. The stress-strain flow curves of the studied materials exhibited a peak followed by a fast drop in stress or sudden failure. A higher peak stress was achieved by decreasing the testing temperature, increasing the strain rate or lowering the amount of binder content. Constitutive equations were used to develop a useful physically based model describing the mechanical resistance of cemented carbides as a function of three different stress terms, representing stresses carried by the binder phase, accommodated by the carbide phase and associated with the interaction between the metallic and ceramic phases. The first term was modelled after the hot deformation of Co and was very small. The second one revealed an activation energy of Q = 585 kJ/mol, identified as that of W pipe diffusion in WC, and was barely dependent on the temperature and strain rate. Finally, the third stress contribution provided valuable insight on the role of the carbide skeleton in cemented carbides, proving the major effect of the microstructural arrangement in the deformation resistance. All the testing conditions were included in the model, with only a few extreme data points having to be excluded. Outcomes of the model were further supported by a thorough EBSD characterization.