The properties of polymer blends are determined to a decisive extent by the morphological structure of the polymer combinations employed. The design of extruders thus calls for models to calculate the estimated morphology development over the length of the extruder screws in the melt-conveying section. Since the most significant morphological changes are observed in the melting section, however, it is also necessary for the morphology formation and development to be analyzed in this section of the extruder. The melting process of binary material combinations is thus important too. In the context of this research, experimental investigations were conducted using polypropylene/polyamide 6 (PP/PA 6). In the tests, the degree of melting and the morphology development were determined over different screws and compared with calculations. In order to analyze a range of relevant influences, the extruder size, screw configuration, screw speed, weight components and also the viscosity ratio were varied by using different PP types. Apart from the model for calculating the melting of polymer blends, a formulation was developed that can be used to estimate the morphological changes occurring in the melt-conveying section. The model is based on the assumption that morphological changes can be estimated by calculating the probabilities of different drop breakup mechanisms and the coalescence process. The investigations of the blend morphology in the melting section and the melt-conveying section reveal key findings that have to be taken into account for modeling the formation and development of the morphology. First of all, in the melting section, it is very clear that a kind of melt film removal occurs at the surface of the granules of the second component, which melts at higher temperatures, as these granules melt. The drops of second component in the melting section, which are directly adjacent to fractions that have not yet fully melted in some cases, have already assumed dimensions (in the μm range) similar to those seen at the end of the extrusion process. This means that, in the melting section of the twin-screw extruder, small volumes are broken or worn off the already-molten granule surfaces. An evaluation of scanning electron micrographs also shows that, in the melting section of co-rotating twin-screw extruders, virtually all the breakup mechanisms that can essentially be distinguished take place in parallel, such as quasi-steady drop breakup or supercritical breakup, folding, end pinching, tip streaming and breakup through capillary instabilities. Alongside the breakup mechanisms, there are also drops that clearly unite to form bigger drops through coalescence. When comparing the calculations for the melting of polymer blends, relatively good agreement is obtained with the experimental test results. The calculations display a satisfactory level of accuracy, particularly for polymer combinations with similar viscosities and also for bigger extruders. The calculations with the morphology model also show the same trends as the experimental investigations. Hence, for the design or optimization of twin-screw extruders, it is now possible not only to calculate the fundamental process variables (such as pressure, temperature, melting) but also to estimate the morphology that has a decisive influence on the resultant material properties.