•Defect-engineering approach to constructing chiral metal-organic frameworks (CMOFs) •One-pot scalable synthesis of CMOFs with high stability and enlarged pore size •Chiral-defect MOFs for high-performance enantioselective sensing The porosity and stability of chiral metal-organic frameworks (CMOFs) are crucial for enantioselective applications. However, coupling these properties by directly assembling metal nodes and chiral linkers is highly challenging. Post-synthetic chiralization provides a facile way to construct CMOFs, but it can decrease pore sizes, which presents a barrier for chiral molecule accommodation. Herein, we have developed a defect-engineering approach to introducing chiral centers and enlarged pores. In contrast to other strategies for synthesizing CMOFs containing large pores, this approach maintains framework stability without additional templates, as demonstrated by the successful preparation of chiral UiO-66, MIL-125-NH2, and MIL-53. Notably, the CMOFs feature high selectivity, record-breaking efficiency, and a broad substrate scope for enantioselective recognition. This study provides a facile and scalable synthetic method for constructing CMOFs with enlarged pores and high stability. The porosity and stability of chiral metal-organic frameworks (CMOFs) are crucial for enantioselective applications. However, coupling these properties by directly assembling metal nodes and chiral linkers is highly challenging. Post-synthetic chiralization provides a facile way to construct CMOFs, but it can decrease pore sizes, which presents a barrier for chiral molecule accommodation. Herein, we have developed a defect-engineering approach to introducing chiral centers and enlarged pores. In contrast to other strategies for synthesizing CMOFs containing large pores, this approach maintains framework stability without additional templates, as demonstrated by the successful preparation of chiral UiO-66, MIL-125-NH2, and MIL-53. Notably, the CMOFs feature high selectivity, record-breaking efficiency, and a broad substrate scope for enantioselective recognition. This study provides a facile and scalable synthetic method for constructing CMOFs with enlarged pores and high stability.