Scientific research increasingly demonstrates that chemicals and materials essential for everyday products threaten natural systems and human health. Transitioning to sustainable, circular, and low-carbon economies depends critically on having safer chemicals available. We propose that materials scientists should also account the impact of the health hazards of chemicals associated with the synthesis, processing, and manufacturing of materials. These include molecular precursors for synthesis of new materials chemistries and chemicals used in various stages of materials processing and manufacturing such as solvents and persistent, accumulative, and highly hazardous. Per- and polyfluoroalkyl substances are examples of harmful chemicals that pose health and environmental risks. A major challenge is finding safer yet functional alternatives that also the meet necessary performance requirements in sustainable materials design and development. The exploration space to discover these is prohibitively large to explore. Hence, we are at a critical inflection point and a paradigm shift is needed to include the development of safer chemicals as part of the equation to accelerate the adoption of safer and more sustainable chemical materials. Using such chemicals as an example, we describe an accelerated data-driven framework for designing safer material chemistries that ensures technical functionality and provide a holistic approach to sustainability.