NiAl-based alloys are promising candidates for high-temperature structural applications but their use is restricted by the limited mechanical properties. However, an improved performance can be achieved by strengthening the NiAl matrix with embedded fibers of refractory metals, such as Cr and Mo. Such composites can be manufactured in-situ by directional solidification of alloys with eutectic composition. For these processes the location of the eutectic trough in the NiAl-Cr-Mo system has to be known. The determination of the respective compositions was achieved by combining experimental investigations with computational thermodynamics. Thus, a series of melts in the NiAl-Cr-Mo system were prepared and their microstructures were investigated after solidification. The information on the primary phases was used to model the liquidus surface of the system NiAl-Cr-Mo using the CALPHAD approach. For this purpose, the thermodynamic datasets of the respective sub-systems from the literature have been combined into a quaternary database. The database will be used in the development of NiAl-based alloys for directional solidification. The dataset allows the calculation of the eutectic temperatures, the phase fractions and further thermodynamic properties along the eutectic trough. The present dataset will provide a reliable description for the NiAl-Cr-Mo system, but other regions of the Al-Cr-Mo-Ni system have an inferior representation.