This book constitutes the refereed proceedings of the 21st Conference on Computability and Logic, CiE 2025, held in Lisbon, Portugal, during July 14-18, 2025. The 27 full papers included in this book were carefully reviewed and selected from 49 submissions. They focus on computability-related science, ranging over mathematics, computer science and applications in various natural and engineering sciences, such as physics and biology, as well as related fields, such as philosophy and history of computing. CiE 2025 had as its motto Crossroads of Computability and Logic: Insights, Inspirations, and Innovations, drawing on the numerous interconnections between computability research and broader logical methodologies, considering both well-established perspectives as well as recent innovations.