Solid–liquid separation is a fundamental operation in process engineering and thus an important part of many process chains in the preparation of slurries in the chemical industry and other parts of the industrial environment. For the separation of micron-sized particles which, due to their size, do not settle or settle very slowly in the earth’s gravity field, centrifuges are often used. The preferred choice are often decanter centrifuges because they work continuously and stabilize the process against product fluctuations due to their adjustment possibilities. The design of the apparatus is complex: The main components of the apparatus are the cylindrical-conical bowl, which rotates at a high speed, and a screw located inside the bowl, which rotates in the same direction at a low differential speed to transport the separated solids out of the apparatus. Geometrical properties of the apparatus, as well as the adjustable operating parameters, such as rotational speed or differential speed, have a significant influence on the separation. In practice, analytical models and the experience of the manufacturers form the basis for the design. Characteristics of the disperse phase, interactions with the liquid, as well as the influence of the flow on the separation, are not taken into account. As a consequence, the transfer to industrial scale always requires a large number of pilot-scale experiments, which are time-consuming and expensive. Due to the increasing computational power, computational fluid dynamics (CFD) provides one possibility to minimize the experimental effort in centrifuge design. In this work, the open-source software OpenFOAM is used to simulate the multi-phase flow in a laboratory decanter centrifuge. For validation, experiments were carried out on a laboratory scale and the main operating parameters, such as speed, differential speed, and volume flow rate, were varied. The simulation results show a good agreement with the experimental data. Furthermore, the numerical investigations show the influence of the flow on the separation of the particles. To evaluate the transportability of a material, the transport efficiency was introduced as a dimensionless parameter. In addition, the simulation allows the consideration of the individual velocity components, making it possible to generate an impression of the complex three-dimensional flow in the apparatus for the first time.