A simple and efficient diffusion couple method is utilized to study the chemical interactions between cemented carbide cutting tools and difficult-to-machine materials (Ti, Ti-6Al-4V, Ni, Inconel 718, Fe, and AISI 316L). The experimental results and simulations probe different chemical interactions between the cemented carbide and work materials. In particular, the formation of a thick TiC layer is observed at the cemented carbide/Ti and Ti-6Al-4V interface while η-phase is formed at the interface between the cemented carbide and work materials Inconel 718, Fe and AISI 316L. Pure titanium and Ti-6Al-4V both interact strongly with the tool causing formation of TiC and dissolution of WC-grains. Experiments and diffusion simulations confirm bcc-W formation and progressive diffusion of W into bcc-Ti. For both Ti and Fe work materials a dense band of carbides (WC + η or WC + TiC) forms at the interface, effectively inhibiting further diffusion. Ni does not form any stable carbide and lowers the η-phase limit in terms of carbon content, wherefore diffusion can occur freely. The diffusion couple method used in this work, corroborated by DICTRA simulations should serve as a useful tool in the detailed analysis of worn tools where chemical wear is dominant.