Polymer processing often activates material degradation, which affects to some extent the performance or the life cycle of the obtained products. Polymer degradation is usually evidenced by molecular weight variations as consequence of exposure to high processing temperature and to relevant mechanical stresses. The degrading effects of melt extrusion under different thermo-mechanical conditions on polymethyl-methacrylate and polystyrene are investigated. Materials were processed at different temperatures and rates in a single screw extruder and in a capillary rheometer. Processed and as-received materials were analysed by Gel permeation chromatography, solution viscosity, and melt rheology. Evaluations of molecular weight and rheological behavior changes after processing, as compared with as-received materials, evidenced the extent of degradation in the different conditions. Experimental analysis was accompanied by finite elements simulation of the polymer flow and heat transmission within the extruder. This allowed an estimation of the expected shear stresses and temperatures distributions, thus indicating potentially critical situations. It was found that the materials processed at the highest rates in extruder presented lowest molecular weight reductions. This was attributed to the shorter residence time in the extruder and to the possibility of wall slip phenomena, which likely reduce the actual shear stress and viscous dissipation in the fast processing conditions.