This book constitutes the proceedings of the 21st International Conference on Foundations of Software Science and Computational Structures, FOSSACS 2018, which took place in Thessaloniki, Greece, in April 2018, held as part of the European Joint Conference on Theory and Practice of Software, ETAPS 2018.The 31 papers presented in this volume were carefully reviewed and selected from 103 submissions. The papers are organized in topical sections named: semantics; linearity; concurrency; lambda-calculi and types; category theory and quantum control; quantitative models; logics and equational theories; and graphs and automata.