Modulating TPP riboswitch activity simultaneously enhances crop yield, nutritional quality and stress tolerance.

While enhancing crop yield remains a critical breeding objective, such efforts often compromise nutritional quality and stress tolerance. The growing global population and increasing environmental stresses make combining stable crop yields with improved nutritional quality a vital objective for sustainable food security. Thiamine pyrophosphate (TPP), the active form of vitamin B1, regulates core metabolism to support both human health and plant stress tolerances. Here, we show that editing the rice TPP riboswitch elevates multiple micronutrients, simultaneously increasing grain yield, cold tolerance, and blast resistance. Mechanistically, these enhancements link to promoted photosynthesis, improved nitrogen use efficiency, and system-wide transcriptional-metabolic reprogramming. Editing homologs in tomato produces similar outcomes, supporting the generalizability of this approach. Thus, modulating TPP levels offers a viable strategy to synergistically boost crop productivity, nutritional quality, and stress tolerance, which are essential for achieving sustainable food security without trade-offs.