Modern chemistry is the backbone of our society, but it is also a major contributor to global environmental pollution and the ongoing climate crisis. The transition toward a sustainable future requires a radical transformation of how chemistry is designed, developed, and used. This represents a “break it or make it” challenge for the chemical industry with significant technology lock-in and high entry barriers to radical innovations. We propose that urgently required systemic changes in chemical industry, research and development (R&D), chemicals assessment and management, and education to advance sustainable chemistry are attainable through increased and more rapid adoption of digitalization and new digital tools. This will enable flexible data exchange, increased transparency of information flows along cross-country chemical, material, and product life cycles, and chemistries that are safe and sustainable by design, addressing the complexity of chemicals-environment-health interactions and lowering the costs of entry into chemical R&D and manufacture, and new, more sustainable and collaborative business models.