The extraordinary property profiles of many biological materials derive from their hierarchical structure and control of order and disorder at different length scales. Application of these concepts to the design of synthetic polymers may provide new routes to lightweight materials that combine high stiffness, strength, and toughness. Here, we use high-temperature reactive melt extrusion to introduce aliphatic substitutional defects into a high-performance semiaromatic copolyamide that are able to conform to the dominant crystalline phase. This allows us to generate microstructural disorder while maintaining or even increasing the macroscopic degree of crystallinity, and hence engineer a strain-induced phase transformation in the resulting polyamides that results in an increase in chain extension along the tensile axis in the crystalline regions. The yield stress and stiffness consequently remain comparable to those of the base semiaromatic polyamide, but the strain-to-failure and tensile toughness increase more than five-fold. Tailoring the concentration and distribution of microstructural defects is hence a straightforward and powerful strategy for optimizing performance in semicrystalline polyamides.