This book constitutes the refereed proceedings of the 35th International Conference on High Performance Computing, ISC High Performance 2020, held in Frankfurt/Main, Germany, in June 2020. The 27 revised full papers presented were carefully reviewed and selected from 87 submissions. The papers cover a broad range of topics such as architectures, networks & infrastructure; artificial intelligence and machine learning; data, storage & visualization; emerging technologies; HPC algorithms; HPC applications; performance modeling & measurement; programming models & systems software. The conference was held virtually due to the COVID-19 pandemic. Chapters "Scalable Hierarchical Aggregation and Reduction Protocol (SHARP) Streaming-Aggregation Hardware Design and Evaluation", "Solving Acoustic Boundary Integral Equations Using High Performance Tile Low-Rank LU Factorization", "Scaling Genomics Data Processing with Memory-Driven Computing to Accelerate Computational Biology", "Footprint-Aware Power Capping for Hybrid Memory Based Systems", and "Pattern- Aware Staging for Hybrid Memory Systems" are available open access under a Creative Commons Attribution 4.0 International