Organic field-effect transistor (OFET) is an ideal sensor platform, which has rich sensing mechanisms for perceiving analytes. Benefiting from the advantages of organic semiconductors such as lightweight, mechanical flexibility, solution processability and tunable molecular structure, various flexible sensors based on OFETs have been widely applied in the fields of wearable electronics, e-skin, biological detection and environmental protection. This review summarizes the research progress of flexible OFET-based sensors in recent years. From the perspective of materials, mechanisms and applications, we introduce the design principle of organic semiconductor sensing materials, the working mechanisms of OFET-based sensors and their applications in the fields of chemistry, biology and physics. In the end, we conclude the current situation and existing problems of OFET-based sensors and look ahead to the future development direction of flexible OFET-based sensors.