This book constitutes the refereed proceedings of the 21st International Conference on Principles and Practice of Multi-Agent Systems, PRIMA 2018, held in Tokyo, Japan, in October/November 2018. The 27 full papers presented and 31 short papers were carefully reviewed and selected from 103 submissions. PRIMA presents subjects in many application domains, particularly in e-commerce, and also in planning, logistics, manufacturing, robotics, decision support, transportation, entertainment, emergency relief and disaster management, and data mining and analytics.