This book constitutes revised selected papers from the 13th International Conference on Large-Scale Scientific Computing, LSSC 23021, which was held in Sozopol, Bulgaria, during June 7-11, 2021. The 60 papers included in this book were carefully reviewed and selected from a total of 73 submissions. The volume also includes two invited talks in full paper length. The papers were organized in topical sections as follows: Fractional diffusion problems: numerical methods, algorithms and applications; large-scale models: numerical methods, parallel computations and applications; application of metaheuristics to large-scale problems; advanced discretizations and solvers for coupled systems of partial differential equations; optimal control of ODEs, PDEs and applications; tensor and matrix factorization for big-data analysis; machine learning and model order reduction for large scale predictive simulations; HPC and big data: algorithms and applications; and contributed papers.