This book constitutes the thoroughly refereed post-conference proceedings of the 6th International Symposium on Combinatorial Optimization, ISCO 2020, which was due to be held in Montreal, Canada, in May 2020. The conference was held virtually due to the COVID-19 pandemic. The 24 revised full papers presented in this book were carefully reviewed and selected from 66 submissions.They were organized in the following topical sections: polyhedral combinatorics; integer programming; scheduling; matching; Network Design; Heuristics.