This book constitutes the thoroughly refereed post-conference proceedings of the 21st International Workshop on Multi-Agent-Based Simulation, MABS 2021, held in May 2021 as part of AAMAS 2021. The conference was held virtually due to COVID 19 pandemic. The 14 revised full papers included in this volume were carefully selected from 23 submissions. The workshop focused on finding efficient solutions to model complex social systems, in such areas as economics, management, organizational and social sciences in general. In all these areas, agent theories, metaphors, models, analysis, experimental designs, empirical studies, and methodological principles, all converge into simulation as a way of achieving explanations and predictions, exploration and testing of hypotheses, better designs and systems and providing decision-support in a wide range of applications.