This book constitutes the proceedings of the 13th International Symposium on NASA Formal Methods, NFM 2021, held virtually in May 2021. The 21 full and 3 short papers presented in this volume were carefully reviewed and selected from 66 submissions. The papers aim to identify challenges and provide solutions to achieve assurance in mission-critical and safety-critical systems. Examples of such systems include advanced separation assurance algorithms for aircraft, next-generation air transportation, autonomous rendezvous and docking of spacecraft, on-board software for unmanned aerial systems (UAS), UAS traffic management, autonomous robots, and systems for fault detection, diagnosis, and prognostics.