This book constitutes the refereed proceedings of the 16th European Conference on Symbolic and Quantitative Approaches to Reasoning with Uncertainty, ECSQARU 2021, held in Prague, Czech Republic, in September 2021. The 48 full papers presented in this volume were carefully reviewed and selected from 63 submissions. The papers are organized in topical sections about argumentation and analogical reasoning, Bayesian networks and graphical models, belief functions, imprecise probability, inconsistency handling and preferences, possibility theory and fuzzy approaches, and probability logic.