Mathematical modeling of the separation process in counter-current decanter centrifuges was performed, taking into account the influence of the sediment build-up and the flow pattern. Thus far, separation processes in centrifuges have been calculated by means of simplified empirical models based on the so-called sigma theory. To reduce experimental efforts, a new model was developed that describes the separation process by considering material functions for sedimentation and the gel point. In addition, an arising sediment build-up and changes in the flow conditions were taken into account. The conducted numerical simulations were validated by experiments. Simplified models such as the sigma theory usually depend on experimental data of industrial machines. The approach presented here shows an enhanced accuracy while not depending on such information. The proposed simulation procedure is adaptable to other types of decanter centrifuges such as co-current machines.