The morphology and mechanical properties of polyamide-based blends prepared in single and corotating twin-screw extruders were compared using transmission electron microscopy (TEM) techniques. Reactive polyamide blends with SEBS-g-MA (a maleated styrenic triblock copolymer with ethylene-butylene midblocks), EPR-g-MA (a maleated ethylene/propylene rubber), and ABS were selected for the purpose of this investigation. For blends of SEBS-g-MA with difunctional (nylon x,y) polyamides (e.g., nylon 6,6; nylon 12,12), the twin-screw extruder was more effective in producing a finer dispersion of the rubber phase, which resulted in a significant lowering of the ductile-brittle transition temperature in case of the nylon 6,6 blend. On the other hand, blends of SEBS-g-MA with the monofunctional nylon 6 material led to rubber particles that were too small for toughening for both extruder types employed in this work. For nylon 6/EPR-g-MA blends, the single-screw extruder led to blends with excellent low-temperature impact properties for both single-step and masterbatch mixing techniques, whereas nylon 6/EPR-g-MA blends prepared in a single-step operation in the twin-screw extruder were brittle under ambient conditions. For difunctional polyamide blends with ABS (compatibilized with an imidized acrylic polymer), the morphology and mechanical properties were found to be independent of the extruder type employed for processing.