This book constitutes the refereed proceedings of the 36th International Conference on High Performance Computing, ISC High Performance 2021, held virtually in June/July 2021. The 24 full papers presented were carefully reviewed and selected from 74 submissions. The papers cover a broad range of topics such as architecture, networks, and storage; machine learning, AI, and emerging technologies; HPC algorithms and applications; performance modeling, evaluation, and analysis; and programming environments and systems software.