This book constitutes the refereed proceedings of the 21st International Workshop on Computer Algebra in Scientific Computing, CASC 2019, held in Moscow, Russia, in August 2019. The 28 full papers presented together with 2 invited talks were carefully reviewed and selected from 44 submissions. They deal with cutting-edge research in all major disciplines of computer algebra. The papers cover topics such as polynomial algebra, symbolic and symbolic-numerical computation, applications of symbolic computation for investigating and solving ordinary differential equations, applications of CASs in the investigation and solution of celestial mechanics problems, and in mechanics, physics, and robotics.