In the past decades, remarkable progress has been achieved in the exploration of electrocatalysts with high activity, long durability, and low cost. Among these, defective graphene (DG)-based catalysts are considered as one of the most potential substitutes for precious metal-based electrocatalysts. DG-based catalysts contain abundant active centers with different configurations resulting from their extraordinary high-structural tunability. Herein, an overview on recent advancements in developing four kinds of DG-based catalysts is presented: 1) heteroatoms-doped graphene; 2) intrinsic DG (vacancy and topological defect); 3) nonmetal atoms or/and metal species-modified intrinsic DG (heterogeneous species and intrinsic defects co-tuned DG); and 4) DG-based van der Waals-type multilayered heterostructures. In particular, the synergistic effects between various defects are discussed, and the origin of catalytic activity is reviewed. Meanwhile, the established defect-derived catalytic mechanism is summarized, which is beneficial for the rational design and fabrication of high-performance electrocatalysts for practical energy-related applications. Finally, challenges and future research directions on defect engineering in noble metal-free materials for electrocatalysis are proposed.